Aggressive Posterior Retinopathy of Prematurity: Clinical and Quantitative Imaging Features in a Large North American Cohort

Abstract

Purpose: Aggressive posterior retinopathy of prematurity (AP-ROP) is a vision-threatening disease with a significant rate of progression to retinal detachment. The purpose of this study was to characterize AP-ROP quantitatively by demographics, rate of disease progression, and a deep learning-based vascular severity score.

Design: Retrospective analysis.

Participants: The Imaging and Informatics in ROP cohort from 8 North American centers, consisting of 947 patients and 5945 clinical eye examinations with fundus images, was used. Pretreatment eyes were categorized by disease severity: none, mild, type 2 or pre-plus, treatment-requiring (TR) without AP-ROP, TR with AP-ROP. Analyses compared TR with AP-ROP and TR without AP-ROP to investigate differences between AP-ROP and other TR disease.

Methods: A reference standard diagnosis was generated for each eye examination using previously published methods combining 3 independent image-based gradings and 1 ophthalmoscopic grading. All fundus images were analyzed using a previously published deep learning system and were assigned a score from 1 through 9.

Main outcome measures: Birth weight, gestational age, postmenstrual age, and vascular severity score.

Results: Infants who demonstrated AP-ROP were more premature by birth weight (617 g vs. 679 g; P = 0.01) and gestational age (24.3 weeks vs. 25.0 weeks; P < 0.01) and reached peak severity at an earlier postmenstrual age (34.7 weeks vs. 36.9 weeks; P < 0.001) compared with infants with TR without AP-ROP. The mean vascular severity score was greatest in TR with AP-ROP infants compared with TR without AP-ROP infants (8.79 vs. 7.19; P < 0.001). Analyzing the severity score over time, the rate of progression was fastest in infants with AP-ROP (P < 0.002 at 30-32 weeks).

Conclusions: Premature infants in North America with AP-ROP are born younger and demonstrate disease earlier than infants with less severe ROP. Disease severity is quantifiable with a deep learning-based score, which correlates with clinically identified categories of disease, including AP-ROP. The rate of progression to peak disease is greatest in eyes that demonstrate AP-ROP compared with other treatment-requiring eyes. Analysis of quantitative characteristics of AP-ROP may help improve diagnosis and treatment of an aggressive, vision-threatening form of ROP.

Figure 1.. Box-plot distribution of vascular severity scores by peak disease severity.

The vascular severity score at the time of peak disease severity for eyes in three cohorts in the Imaging and Informatics in retinopathy of prematurity (ROP) cohort study was significantly different for each disease category including treatment-requiring (TR) disease with aggressive posterior retinopathy of prematurity (AP-ROP, p<0.001 for all comparisons).

Figure 2.. Longitudinal evaluation of vascular severity score.

Violin plot distribution of vascular severity score for eyes in three cohorts in the Imaging and Informatics in retinopathy of prematurity (ROP) cohort study. Number (n) in each cohort as well as median and interquartile-range (IQR) of vascular severity score at each time point displayed below. Eyes with aggressive posterior retinopathy of prematurity (AP-ROP) demonstrated earlier and more rapid progression of disease severity compared to treatment-requiring (TR) eyes without AP-ROP and those eyes with non-TR ROP (p<0.002 for 30-32 weeks, and p<0.001 for all other time points).

Figure 3.. Representative fundus photos and vascular severity scores of eyes with and without aggressive posterior retinopathy of prematurity (AP-ROP).

Three example images from eyes of patients with and without AP-ROP. A) Left eye of an infant with type 2 ROP. On ophthalmoscopy, this patient had zone II, stage 2 disease with pre-plus and a severity score of 4.1. B) Right eye of an infant with treatment-requiring (TR) ROP. On ophthalmoscopy, this infant was diagnosed with zone 2, stage 3 disease with plus disease. C) Left eye of an infant diagnosed with TR-ROP with AP-ROP. On ophthalmoscopy, this patient was diagnosed with zone 1, stage 3 with plus disease. Compared to the baby in B, the baby in C demonstrated extensive flat stage 3 disease rather than the more typical stage configuration seen in B.