Vitreoretinal biomarkers of retinopathy of prematurity using handheld optical coherence tomography: a review

Abstract

Retinopathy of prematurity (ROP) is caused by abnormal retinal vascularization in premature infants that has the potential for severe long-term vision impairment. Recent advancements in handheld optical coherence tomography (OCT) have enabled noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. The use of handheld OCT devices in the diagnosis of ROP in premature infants has furthered our understanding of disease state and progression. This review discusses the known and novel biomarkers of ROP severity in premature infants identified through handheld OCT and potential for future directions.

Keywords: childhood blindness; handheld optical coherence tomography; plus disease; preterm infant; retinopathy of prematurity (ROP); vison screening; vitreoretinal biomarkers.

Figure 1

Handheld OCT devices. (A) Envisu C2300 handheld spectral domain optical coherence tomography (Leica Microsystems, Germany). (B) Model for investigational handheld swept source optical coherence tomography from the University of Washington Department of Bioengineering. This device has a handheld screen which features live video of the pupil and B-scan OCT images.

Figure 2

Handheld spectral domain optical coherence tomography images obtained from premature infants showing vitreous biomarkers of retinopathy of prematurity. (A) Numerous punctate hyperreflective vitreous opacities (circled) hovering above the retina are demonstrated in a premature infant with Stage 3 retinopathy of prematurity. (B) A tractional vitreous band (arrowheads) approaches at a steep angle, making contact with the retina near the fovea. Punctate hyperreflective vitreous opacities above the retina are also shown in a premature infant with Stage 3 retinopathy of prematurity. (C) Another example of a vitreous band (arrowheads) in a premature infant with Stage 0 retinopathy of prematurity.

Figure 3

Handheld swept source optical coherence tomography images with variable foveal maturity. (A) Persistent inner retinal layers (orange bracket) and the absence of an ellipsoid zone with a relatively thin choroid at the fovea in the right eye of a premature infant (birth weight 629 g; gestational age 23 5/7 weeks) imaged at postmenstrual age of 36 5/7 weeks. (B) Normal inner retinal layers with an ellipsoid zone (orange line) present with a relatively thick choroid at the fovea in the left eye of a full term infant (birth weight 3509 g; gestational age 36 weeks) imaged at postmenstrual age of 36 1/7 weeks.

Figure 4

Handheld swept source optical coherence tomography images obtained from premature infants demonstrated that thinner choroid is associated with higher retinopathy of prematurity stage, worse plus disease, lower gestational age, and lower birth weight. (A) Swept source optical coherence tomography of a premature infant with Stage 2 retinopathy of prematurity, without plus disease and (B) Another infant with Stage 0 retinopathy of prematurity and no plus disease demonstrates thicker choroid.

Figure 5

Handheld spectral domain optical coherence tomography images of dome-shaped maculae in premature infants. Dome-shaped macula was seen in 24 of 37 (65%) premature infants undergoing retinopathy of prematurity screening. Their presence was associated with low birth weight, plus disease, and a diagnosis of retinopathy of prematurity. (A) An example of subtle dome-shaped macula in a premature infant (birth weight 1210 g; gestational age 28 6/7 weeks) imaged at postmenstrual age of 35 1/7 weeks. (B) An example of more prominent dome-shaped macula seen in a premature infant (birth weight 499 g; gestational age 27 1/7 weeks) imaged at postmenstrual age of 40 weeks.

Figure 6

Vascular abnormality score on OCT features. (A) Handheld spectral domain optical coherence tomography image demonstrating hyporeflective vessels and vessel elevation (orange asterisk) in the right eye of a premature infant with zone III, Stage 3 retinopathy of prematurity with pre-plus disease (birth weight 1310 g, gestational age 31 2/7 weeks) imaged at postmenstrual age of 41 1/7 weeks. (B) Handheld swept source optical coherence tomography image demonstrating retinal space (orange arrow) in the right eye of a premature infant with zone II, stage 0 retinopathy of prematurity with plus disease (birth weight 1098 g; gestational age 30 2/7 weeks) imaged at postmenstrual age of 34 2/7 weeks. (C) Handheld spectral domain optical coherence tomography image demonstrating scalloped retinal layers (thick orange line — inner plexiform layer; thin orange line — outer plexiform layer) in the right eye of a premature infant with zone III, stage 3 retinopathy of prematurity with plus disease (birth weight 1310 g, gestational age 31 2/7 weeks) imaged at postmenstrual age of 46 1/7 weeks.

Figure 7

OCT angiogram demonstrating the foveal avascular zone in the right eye of a premature infant with zone II, stage 0 retinopathy of prematurity (birth weight 636 g; gestational age 27 0/7 weeks) imaged at postmenstrual age 36 0/7 weeks. En face OCT flow images (A–C) and en face OCT structural images (D–F) of superficial retinal layer (SRL), deep retinal layer (DRL) and superficial and deep retinal layers.

Figure 8

Peripheral optical coherence tomography retinal (OCT) images. (A) En face volumetric ultra-wide field OCT image of a premature infant with zone II, mild stage 2 retinopathy of prematurity (birth weight 690 g; gestational age 24 1/7 weeks) and (B) Another premature infant with zone I, stage 2 with popcorn neovascularization retinopathy of prematurity (birth weight 622 g; gestational age 24 1/7 weeks). (Courtesy of Peter Campbell, MD and Yifan Jian, PhD).