Abstract
Purpose :
Retinopathy of prematurity (ROP) is a disease of abnormal vascular development in premature infants that potentially leads to blindness. A finding of tortuous and dilated vessels or plus disease during dilated retinal exams indicates severe disease requiring treatment. However, it is difficult to distinguish arteries from veins. Treatment could be delayed due to the discrepancies in subjective diagnosis of ROP amongst experts. Using fluorescein angiography (FA), arterio-venous abnormalities were distinguished and quantified throughout vascular development in live OIR mice.
Methods :
48 newborn C57BL/6J mice were exposed to 77±2% oxygen from postnatal day (P)7 till P12. 48 mice were raised in room air (RA). In vivo FA was performed at early (P16 to P18), mid (P23 to P25), and late (P30 to P32) phases of retinal vascular development. Retinal artery tortuosity (RAT), retinal vein width (RVW), and retinal vascular area (RVA) were quantified. Values are given as mean ±SD.
Results :
OIR mice had patchy areas of capillary vaso-obliteration unlike the uniform capillary network in RA mice, so that percent RVA in total image area was reduced in early phase (19.31±7.91,n=16) in OIR mice compared to RA (31.56±10.81, n=16,p=0.003). RVA in OIR mice increased from early to mid-phase (p<0.0001), but was smaller and sparser than RA at late phase (p=0.0249) despite full capillary coverage. RVW was higher in OIR (60.76±12.2µm,n=16) than RA mice in early phase (40.21±4.8µm,n=16 p<0.0001) and mid phase (p=0.041), but were equivalent by late phase (p=0.96). OIR mice were more tortuous arteries than RA mice in early (1.22±0.12 vs 1.003±0.003, p<0.0001), mid (1.1±0.06 vs 1.003±0.002, p<0.0001), and late (1.07±0.12 vs 1.002±0.003, p< 0.004) phases of retinal vascular development. RA mice maintained uniform RVA, RVW, and RAT in all phases.
Conclusions :
In vivo FA distinguishes arterial and venous abnormalities and reveals persistent retinal artery tortuosity in adult OIR mice. RAT may be a reliable, objective marker of ROP severity and progression during clinical diagnosis of plus disease. Clinical application of objective methods would facilitate earlier detection, more consistent diagnosis, earlier treatment, and closer monitoring of ROP to avoid adverse visual outcomes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.