Spectral Domain Optical Coherence Tomography correlates Retinal Thinning to Retinal Vascular Development in an In vivo Mouse Model of Retinopathy of Prematurity

Background Retinopathy of Prematurity (ROP) is a condition of abnormal retinal vascular development affecting premature infants, exacerbated by exposure to hyperoxia due to lung immaturity. Fluorescein angiography (FA) in live anesthetized mice has been used to depict various phases (early, mid, late, and mature) of retinal vascular development (RVD). Spectral domain optical coherence tomography (SD‐OCT) allows in vivo study of retinal structure; but retinal structural abnormalities in ROP have not been well elucidated. In this study, i n vivo FA and SD‐OCT were used to study retinal thickness changes in the different phases of RVD. Method 63 mice were exposed to 77% oxygen from postnatal (P) day7‐P12 to induce oxygen‐induced retinopathy (OIR), while 63 mice were raised in room air (RA). Simultaneous FA and SD‐OCT were performed using the Micron IV retinal imaging device. Mean total retinal thickness (TRT), inner retinal thickness (IRT), and outer retinal thickness (ORT) were calculated in RA and OIR mice at early (P19), mid (P24), late (P32), and mature (P47) phases of retinal vascular development. Results At P19, the TRT was higher in RA (197.57±3.49μm, n=14) compared to OIR mice (162.66±17.75μm, n=13, P<0.0001). TRT in OIR mice remained reduced at P24(P<0.0001), P32(P<0.0001), and P47(P<0.0001) compared to RA mice. There was no difference between the ORT in RA (94.51±1.81μm) and OIR mice (91.06±6.44μm, p=0.08) at P19 and from P24 to P47(P>0.2). IRT was significantly reduced in OIR (71.60±17.14μm) compared to RA (103.07±3.47μm, P<0.0001) mice at P19, P24 (P<0.0001), P32 (P<0.0001), and P47 (P<0.0001). There was no change in IRT in OIR mice going from P19 up to P47 (P>0.1). IRT was decreased in RA mice from P19 to P24 (p<0.0001) and from P24 to P32 (P=0.02), but remained stable from P32 to P47 (P>0.5). At P47, the IRT was still thinner in OIR compared to RA mice (P<0.0001). Conclusion We have elucidated the natural progression of retinal structural changes in OIR using simultaneous in vivo SD‐OCT and FA. Total retinal thickness was significantly decreased in adult OIR mice from post‐natal oxygen exposure during retinal vascular development compared to RA mice. Retinal thinning in OIR mice occurred specifically in the inner retina during early phase RVD, which persisted in mature phase RVD. RA mice had a physiologic decrease in inner retinal thickness with age up to P32, and then thickness was preserved from late to mature phase RVD. Our study suggests likely significant apoptosis or atrophy of the inner retina in ROP, which persists despite revascularization of the capillary network. Further in vivo structural studies will aid understanding of the patho‐physiology of ROP, disease progression, and functional implications of structural abnormalities. Support or Funding Information Department of Pediatrics, University of Wisconsin, MadisonGraduate School, University of Wisconsin, MadisonCentennial Scholars Program Award, University of Wisconsin, MadisonNational Eye Institute NIHLRP