Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study.

Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.

Ocular Pigmentation Impact on Retinal Versus Choroidal Optical Coherence Tomography Imaging in Preterm Infants.

Purpose: To evaluate the association of fundus pigmentation with the visibility of retinal versus choroidal layers on optical coherence tomography (OCT) in preterm infants. Methods: For infants enrolled in BabySTEPS, ophthalmologists recorded fundus pigmentation (blond, medium, or dark) at the first retinopathy of prematurity (ROP) examination. Bedside OCT imaging was performed at each examination, and a masked grader evaluated all OCT scans from both eyes of each infant for visibility (yes/no) of all retinal layers and of the chorio-scleral junction (CSJ). Multivariable logistic regression was used to assess associations between fundus pigmentation and visibility of all retinal layers and CSJ, controlling for potential confounders (i.e., birth weight, gestational age, sex, OCT system, pupil size, and postmenstrual age at imaging). Results: Among 114 infants (mean birth weight, 943 grams; mean gestational age, 27.6 weeks), 43 infants (38%) had blond, 56 infants (49%) had medium, and 15 infants (13%) had dark fundus pigmentation. Of 1042 scans, all retinal layers were visible in 977 (94%) and CSJ in 895 (86%). Pigmentation was not associated with retinal layer visibility (P = 0.49), but medium and dark pigmentation were associated with decreased CSJ visibility (medium: odds ratio [OR] = 0.34, P = 0.001; dark: OR = 0.24, P = 0.009). For infants with dark pigmentation, retinal layer visibility increased (OR = 1.87 per week; P ≤ 0.001) and CSJ visibility decreased (OR = 0.78 per week; P = 0.01) with increasing age. Conclusions: Although fundus pigmentation was not associated with the visibility of all retinal layers on OCT, darker pigmentation decreased CSJ visibility, and this effect increased with age. Translational Relevance: The ability of bedside OCT to capture retinal layer microanatomy in preterm infants, regardless of fundus pigmentation, may represent an advantage over fundus photography for ROP telemedicine.

Biphasic change in retinal nerve fibre layer thickness from 30 to 60 weeks postmenstrual age in preterm infants.

BACKGROUND/AIMS: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants. METHODS: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA. RESULTS: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 µm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 µm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 µm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 µm/week (95% CI: -0.9 to -0.6). CONCLUSION: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

Semi-automated vessel analysis of en face posterior pole vessel maps generated from optical coherence tomography for diagnosis of plus or pre-plus disease.

En face retinal vessel maps generated from bedside optical coherence tomography (OCT) can show posterior pole vascular tortuosity and dilation (ie, plus/pre-plus disease). In this proof-of-concept study, we found that ROPtool could trace OCT-generated retinal vessel maps with high reliability and accuracy for detecting plus or pre-plus disease.

Association Between Retinal Microanatomy in Preterm Infants and 9-Month Visual Acuity.

Importance: Preterm infants are at risk for poor visual acuity (VA) outcomes, even without retinal problems on ophthalmoscopy. Infant retinal microanatomy may provide insight as to potential causes. Objective: To evaluate the association between preterm infant retinal microanatomy and VA at 9 months' corrected age. Design, Setting, and Participants: This prospective observational study took place from November 2016 and December 2019 at a single academic medical center and included preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS). Infants were eligible for enrollment in BabySTEPS if they met criteria for retinopathy of prematurity (ROP) screening, were 35 weeks' postmenstrual age or older at the time of first OCT imaging, and a parent or guardian provided written informed consent. Of 118 infants enrolled in BabySTEPS, 61 were included in this analysis. Data were analyzed from March to April 2021. Exposures: Bedside optical coherence tomography (OCT) imaging at a mean (SD) 39.85 (0.79) weeks' postmenstrual age and monocular grating VA measurement at 9 months' corrected age. Main Outcomes and Measures: Presence and severity of macular edema and presence of ellipsoid zone at the fovea measured by extracting semiautomated thicknesses of inner nuclear layer, inner retina, and total retina at the foveal center; choroid across foveal 1 mm; and retinal nerve fiber layer (RNFL) across the papillomacular bundle (PMB). Pearson correlation coefficients were calculated and 95% CIs were bootstrapped for the association between retinal layer thicknesses and continuous logMAR VA. Associations were analyzed between retinal microanatomy and normal (3.70 cycles/degree or greater) vs subnormal grating VA at 9 months' corrected age using logistic regression and with logMAR VA using linear regression, adjusting for birth weight, gestational age, and ROP severity at the time of OCT imaging and accounting for intereye correlation using generalized estimating equations. Results: The mean (SD; range) gestational age of included infants was 27.6 (2.8; 23.0-34.6) weeks, and mean (SD; range) birth weight was 958.2 (293.7; 480-1580) g. In 122 eyes of 61 infants, the correlations between retinal layer thicknesses and logMAR VA were as follows: r, 0.01 (95% CI, -0.07 to -0.27) for inner nuclear layer; r, 0.19 (95% CI, 0.01 to 0.35) for inner retina; r, 0.15 (95% CI, -0.02 to 0.31) for total retina; r, -0.22 (95% CI, -0.38 to -0.03) for choroid; and r, -0.27 (95% CI, -0.45 to 0.10) for RNFL across the PMB. In multivariable analysis, thinner RNFL across the PMB (regression coefficient, -0.05 per 10-µm increase in RNFL thickness; 95% CI, -0.10 to -0.01; P = .046) and prior ROP treatment (regression coefficient, 0.33 for ROP treatment; 95% CI, 0.11 to 0.56; P = .003) were independently associated with poorer 9-month logMAR VA. Conclusions and Relevance: In preterm infants, RNFL thinning across the PMB was associated with poorer 9-month VA, independent of birth weight, gestational age, need for ROP treatment, and macular microanatomy. Evaluation of RNFL thickness using OCT may help identify preterm infants at risk for poor vision outcomes.

Integrated Visualization Highlighting Retinal Changes in Retinopathy of Prematurity From 3-Dimensional Optical Coherence Tomography Data.

Importance: Early diagnosis of plus disease is critical in the management of retinopathy of prematurity (ROP). However, there is substantial interexpert disagreement in the diagnosis of plus disease based on vascular changes alone. Information derived from optical coherence tomography (OCT) may help characterize the severity of vascular and structural abnormalities in ROP. Objective: To describe integrated visualization of 3-dimensional (3-D) data from investigational swept-source OCT optimized to delineate retinal vascular and microanatomical features in eyes with and without ROP. Design, Setting, and Participants: This cross-sectional, observational report of OCT was captured in the prospective Study of Eye Imaging in Preterm Infants (BabySTEPS) designed in July 2016 at the Duke Health Intensive Care Nursery. Between December 2018 and August 2019, 2 preterm infants born at 24 and 30 weeks' gestation were enrolled, underwent ROP screening, and were imaged at those screening visits. Data at 36 weeks' postmenstrual age were analyzed via this visualization developed between September 2020 and May 2021. Main Outcomes and Measures: Superimposed en face retinal vascular shadow view (RVSV) montages and thickness maps were used along with OCT B-scans to evaluate retinal vasculature and cross-section in eyes with and without ROP. Results: In the right eyes of 2 infants, 3-D data were integrated and visualized from investigational bedside OCT imaging at the posterior pole. In the infant who developed type 1 ROP, RVSV-OCT confirmed presence of dilated and tortuous posterior pole vessels, shunting, and incomplete perifoveal vascular development, resulting in a temporal notch of avascular retina in zone 1. The thickness map revealed irregular pockets of thickening and thinning, and integrated visualization outlined the demarcation between thicker vascularized retina and thinner avascular fovea and presence of extraretinal neovascularization overlying elevated vessels in the superior arcades. In the infant without ROP (stage 0), RVSV-OCT revealed no abnormal vascular findings at the posterior pole. The integrated visualization showed a dome-shaped retinal thickening at the fovea, which was confirmed as macular edema. Conclusions and Relevance: In 2 preterm infants in BabySTEPS, 3-D visualization of OCT findings during the ongoing ROP disease process demonstrated supplemental information about the retinal vasculature and microanatomy that can be useful to clinicians. These additional details provided by OCT could be integrated into future ROP screening methods with artificial intelligence-based analytics.

Slow progressive perifoveal vascular formation in an infant with aggressive posterior retinopathy of prematurity.

Aggressive posterior retinopathy of prematurity (AP-ROP) is a severe form of ROP occurring in preterm infants that is characterized by rapid progression and prominent vascularity. We report the use of investigational bedside noninvasive optical coherence tomography angiography to visualize the slow and progressive perifoveal vascular formation in an infant with AP-ROP treated with bevacizumab. We also document extensive vascular shunts and morphological differences between arrested and growing retinal capillaries at the vascular wavefront.

Auto-Processed Retinal Vessel Shadow View Images From Bedside Optical Coherence Tomography to Evaluate Plus Disease in Retinopathy of Prematurity.

Purpose: To describe the creation of en face retinal vessel shadow view (RVSV) optical coherence tomography (OCT) images and assess the feasibility of using these for evaluating vascular disease in preterm infants at risk for retinopathy of prematurity (ROP). Methods: In this exploratory study, we selected images from eyes with a range of ROP vascular disease, prospectively acquired from preterm infants using an investigational, noncontact, handheld, bedside swept-source OCT. We autosegmented OCT volumes using custom infant-specific software, extracted RVSV-OCT images from volumetric data bracketed around the retinal pigment epithelium, and automontaged the resulting RVSV-OCT images. Three masked ophthalmologists graded the RVSV-OCT montages as plus, pre-plus, or neither and ranked them by relative vascular disease severity. Results: We selected images from 17 imaging sessions (7 plus, 4 pre-plus, 6 neither on clinical examination). On review, 15/17 (88%) RVSV-OCT montages were gradable for plus, pre-plus, or neither and all 17 montages were rankable for relative severity. Intergrader agreement for plus, pre-plus, or neither grading was good (κ, 0.67; 95% confidence interval, 0.42-0.86) and for relative severity ranking was excellent (intraclass correlation coefficient, 0.98; 95% confidence interval, 0.96-0.99). Conclusions: Our novel automatic processing method can create RVSV-OCT montages optimized for retinal vessel visualization for ROP screening. Although our data support the feasibility of using RVSV-OCT montages for ranking relative vascular disease severity, there is room for improved OCT image capture and processing methods in preterm infants screened for ROP. Translational Relevance: Creation and grading of RVSV-OCT images could eventually be integrated into an alternative method for ROP screening.