Advances in understanding and management of retinopathy of prematurity

Abstract

The understanding, diagnosis, and treatment of retinopathy of prematurity have changed in the 70 years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that retinopathy of prematurity differs in appearance worldwide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe retinopathy of prematurity, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied.

Keywords: angiogenesis; erythropoietin; insulin-like growth factor–1; oxidation or oxidative; oxygen; retinopathy of prematurity; severe ROP; vascular development; vascular endothelial growth factor; vasoproliferation.

Figure 1

Retinal flat mounts of oxygen-induced retinopathy: (Top) Mouse and (Bottom) Rat. (courtesy of James Gilman, CRA, FOPS)

Figure 2

(A) Stage 1 ROP has a white line at the junction of vascularized and avascularized retina. (B) Stage 2 ROP demonstrates a ridge at the junction of vascularized and avascularized retina. (provided by Cyrie Fry, CRA, OCT-C)

Figure 3

Forms of Severe ROP (A). Stage 2 ROP with Plus disease; (B) Stage 3 ROP in posterior Zone II appears as flat neovascularization at the junction of vascular and avascular retina; (C) Stage 3 ROP in peripheral severe ROP in Zone 2 at the junction in peripheral severe ROP. (provided by Cyrie Fry, CRA, OCT-C)

Figure 4

(A) Exudative Stage 4 ROP in left eye; (B) Tractional Stage 4 ROP shown nasally in left eye. (provided by Cyrie Fry, CRA, OCT-C)

Figure 5

Contact imaging following laser can be helpful to identify skip areas, where there is no laser. (courtesy of James Gilman, CRA, FOPS)

Figure 6

Outlined area shows where subsequent laser was performed after initial treatment that led to regression of flat neovascularization. Staged laser up to flat neovascularization in APROP avoids vitreous hemorrhage. Later with regression, additional laser is necessary to prevent subsequent vasoproliferation. (courtesy of James Gilman, CRA, FOPS)

Figure 7

The preterm infant eye is smaller than the adult with <1mm zone to enter the vitreous cavity without causing a retinal break or injury to the lens. (courtesy of James Gilman, CRA, FOPS)

Figure 8

(A) Stage 4A–B ROP shows elevated retina involving the temporal arcade; (B) Following lens-sparing vitrectomy and removal of vitreo-retinal tractional components without retinotomy, the retina settles back. (courtesy of James Gilman, CRA, FOPS)

Figure 9

Oxyhemoglobin dissociation curve. Fetal hemoglobin (HbF) has a curve to the left of adult hemoglobin (HbA). (courtesy of James Gilman, CRA, FOPS)