Simultaneous Fluorescein Angiography and Spectral Domain Optical Coherence Tomography Correlate Retinal Thickness Changes to Vascular Abnormalities in an In Vivo Mouse Model of Retinopathy of Prematurity

Abstract

Background Retinopathy of prematurity (ROP) is a condition of abnormal retinal vascular development (RVD) in premature infants. Fluorescein angiography (FA) has depicted phases (early, mid, late, and mature) of RVD in oxygen-induced retinopathy (OIR) mice. We sought to establish the relationship between retinal structural and vascular changes using simultaneous FA and spectral domain optical coherence tomography (SD-OCT). Method 63 mice were exposed to 77% oxygen at postnatal day 7 (P7) for 5 days, while 63 mice remained in room air (RA). Total retinal thickness (TRT), inner retinal thickness (IRT), and outer retinal thickness (ORT) were calculated at early (P19), mid (P24), late (P32), and mature (P47) phases of RVD. Results TRT was reduced in OIR (162.66 ± 17.75 μm, n = 13) compared to RA mice at P19 (197.57 ± 3.49 μm, n = 14), P24, P32, and P49 (P < 0.0001). ORT was similar in RA and OIR mice at all ages (P > 0.05). IRT was reduced in OIR (71.60 ± 17.14 μm) compared to RA (103.07 ± 3.47 μm) mice at P19 and all ages (P < 0.0001). Conclusion We have shown the spatial and temporal relationship between retinal structure and vascular development in OIR. Significant inner retinal thinning in OIR mice persisted despite revascularization of the capillary network; further studies will elucidate its functional implications in ROP.

Comparison of Neuroprotective Effects of Monomethylfumarate to the Sigma 1 Receptor Ligand (+)-Pentazocine in a Murine Model of Retinitis Pigmentosa

“…The inner retina was measured from the upper edge of the inner limiting membrane to the lower edge of the inner nuclear layer. Outer retina was measured from the lower inner nuclear layer edge to the inferior boundary of the RPE layer; if there was separation of photoreceptors from RPE, we obtained outer retinal thickness by adding the RPE layer thickness and the distance from the lower edge of the inner nuclear layer to the edge of neuronal retina as described 29,33.…”

Simultaneous assessment of aberrant retinal vascularization, thickness, and function in an in vivo mouse oxygen-induced retinopathy model

“…After ERG, simultaneous FA and SD-OCT were performed as previously described [18]. The mice pupils were dilated with 1% tropicamide (Bausch + Lomb, Inc., Tampa, FL), and 10% sodium fluorescein (100 mg/kg) (AK-FLUOR, Akorn, Decatur, IL) was injected IP.…”

“…1b) was obtained like previously reported [17]. After image acquisition, semi-automated segmentations using the Micron IV system's Insight software were made to delineate the total, outer, and inner retinal areas [18]. Each SD-OCT image was converted into a retinal thickness color map ( Fig.…”

“…In an earlier study using SD-OCT in OIR mice after hyperoxia exposure, their retinas were observed to have thinner total cross-sectional width than room air (RA) mice, and avascular retinal areas were shown to be thinner than hypovascular retinal areas [17]. Later in vivo SD-OCT studies revealed that retinal thinning in OIR mice was localized to the inner retina, and was more prominent in the avascular areas [18]. Electroretinogram (ERG) is a commonly used measure of retinal function, but considerable variations in parameters tested (amplitudes, peak times, oscillatory potentials), location tested (focal versus full-field), or flash intensities (low vs medium vs high) make direct comparisons challenging.…”

“…Electroretinogram (ERG) is a commonly used measure of retinal function, but considerable variations in parameters tested (amplitudes, peak times, oscillatory potentials), location tested (focal versus full-field), or flash intensities (low vs medium vs high) make direct comparisons challenging. Whereas noninvasive studies of retinal vascular [5,14] and structural [17,18] development in OIR mice have been shown, simultaneous vascular, structural and functional imaging in the same live animal has not been demonstrated. In this study, we explored whether retinal vascular abnormalities correspond to thickness changes and functional outcomes.…”