Olachi J. Mezu-Ndubuisi

In vivo retinal vascular oxygen tension imaging and fluorescein angiography in the mouse model of oxygen-induced retinopathy.

PURPOSE Oxygenation abnormalities are implicated in the development of retinopathy of prematurity (ROP). The purpose of this study is to report in vivo retinal vascular oxygen tension (PO2) measurements and fluorescein angiography (FA) findings in the mouse model of oxygen-induced retinopathy (OIR). METHODS We exposed 19 neonatal mice to 77% oxygen from postnatal day 7 (P7) to P12 (OIR), while 11 neonatal mice were kept under room air (control). Using phosphorescence lifetime imaging, retinal vascular PO2 was measured followed by FA. Repeated measures ANOVA was performed to determine the effects of blood vessel type (artery and vein) and group (OIR and control) on PO2. Avascular retinal areas were measured from FA images in OIR mice. RESULTS There was a significant effect of vessel type on PO2 (P < 0.001). The effect of group on PO2 was not significant (P = 0.3), indicating similar PO2 between OIR and control mice. The interaction between group and vessel type was significant (P = 0.03), indicating a larger arteriovenous PO2 difference in OIR mice than control mice. In control mice, FA displayed normal vascularization, while FA of OIR mice showed abnormalities, including dilation and tortuosity of major retinal blood vessels, and avascular regions. In OIR mice, the mean percent avascular retinal area was 33% ± 18%. CONCLUSIONS In vivo assessment of retinal vascular oxygen tension and vascularization patterns demonstrated abnormalities in the mouse model of OIR. This approach has the potential to improve understanding of retinal vascular development and oxygenation alterations due to ROP and other ischemic retinal diseases.

Patent Ductus Arteriosus in Premature Neonates

Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a haemodynamically significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation and increase the risk of bronchopulmonary dysplasia, intraventricular haemorrhage, renal dysfunction, cerebral palsy and mortality. We review the pathophysiology, clinical features and assessment of haemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as for rescue therapy to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus, both modalities are associated with significant adverse effects. Because the ductus does undergo spontaneous closure in some premature infants, improved and early identification of infants most likely to develop a symptomatic PDA could help in directing treatment to the at-risk infants and allow others to receive expectant management.

In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery

Purpose Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging. Methods Using fluorescein angiography (FA), retinal vascular features were quantified in live mice with oxygen induced retinopathy (OIR). A total of 105 wild-type mice were exposed to 77% oxygen from postnatal day 7 (P7) till P12 (OIR mice). Also, 105 age-matched pups were raised in room air (RA mice). In vivo FA was performed at early (P16 to P20), mid (P23 to P27), late (P30 to P34), and mature (P47) phases of retinal vascular development. Retinal vascular area, retinal vein width, and retinal artery tortuosity were quantified. Results Retinal artery tortuosity was higher in OIR than RA mice at early (p < 0.0001), mid (p < 0.0001), late (p < 0.0001), and mature (p < 0.0001) phases. Retinal vascular area in OIR mice increased from early to mid-phase (p < 0.0001), but remained unchanged from mid to late (p = 0.23), and from late to mature phase (p = 0.98). Retinal vein width was larger in OIR mice compared to RA mice during early phase only. Arteries in OIR mice were more tortuous from early to mid-phase (p < 0.0001), but tortuosity remained stable from mid through mature phase. RA mice had an increase in retinal vascular area from early to late phase, but maintained uniform retinal vein width and retinal artery tortuosity in all phases. Conclusions In vivo FA distinguished arterial and venous features, similar to plus disease, and revealed aberrant recovery of OIR mice (arterial tortuosity, reduced capillary density, and absent neovascular buds) that persisted into adulthood. Retinal artery tortuosity may be a reliable, objective marker of severity of ROP. Infants with abnormal retinal vascular recovery may need extended monitoring.

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

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.

Minimal Enteral Feeding

In preterm infants, enteral feeding is often delayed by hours to days after birth for fear of feeding intolerance due to immaturity, to avoid the accentuation of hypoxic/ischemic intestinal injury that might have been sustained in utero due to maternal risk factors such as pre-eclampsia, placental inusufficiency, or chorioamnionitis, or after birth due to the presence of cardio respiratory compromise in the early neonatal period, and as a protective strategy to reduce the risk of necrotizing enterocolitis. However, some degree of luminal nutrient exposure is essential to prevent intestinal mucosal atrophy. Minimal enteral feeding is a clinical compromise where small volumes of maternal milk or formula, typically 12–24 mL/kg/day, are provided to avoid complete enteral fasting for prolonged periods. Although preclinical and observational human studies indicate that minimal enteral feeding is likely to be beneficial through maturation of gut motility, induction of gut hormones, and prevention of adverse effects of enteral fasting and parenteral nutrition on the mucosa, randomized clinical trials conducted thus far have not provided conclusive evidence to confirm these benefits. Current clinical evidence suggests that minimal enteral feeding is relatively safe and does not increase incidence of NEC. However, the amount, duration, and the rate of advancement of minimal enteral feeding remain controversial. There is a need for a large, multi-centric study with pre-defined statistical and clinical definitions to draw strong conclusions. In this chapter, we review the physiological rationale and appraise the quality of existing evidence to support minimal enteral feeding in the neonatal intensive care unit.

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

BackgroundRetinopathy of prematurity is a condition of abnormal retinal vascularization in premature infants. The effect of abnormal vascularization on retinal structure and function is unclear. In vivo studies of retinal vascularization, thickness, and function were performed in mice with oxygen-induced retinopathy (OIR mice).MethodsEighteen mice were exposed to hyperoxia at postnatal day (P) 7, whereas 18 mice were raised in room air (RA). At P20 and 40, electroretinogram was performed for a-wave and b-wave amplitudes and peak times, followed by simultaneous fluorescein angiography for retinal avascular area, arterial tortuosity, and vein dilation assessments, and spectral domain optical coherence tomography for retinal thickness.ResultsCapillary density appeared sparser in OIR mice, but retinal avascular area similar to RA mice. Retinal artery tortuosity was higher at P20 and P40 (P = 0.0001) in OIR than RA mice. OIR mice had dilated retinal veins at P20 and thinner inner retinas at P40. Retinal vein width positively correlated with inner retinal thickness (P = 0.008). b-wave amplitude was decreased in avascular retinal areas, and correlated with inner retinal thinning. b-wave peak time was prolonged in adult OIR mice at high intensities (P = 0.03).ConclusionsFocal variations in retinal vascularization of OIR mice correlate with thickness and function. Adult OIR mice had increased retinal artery tortuosity, prolonged b-wave peak time, and decreased retinal vein width with inner retina attrition. These suggest abnormalities in inner retinal morphology or post-receptor signaling. Studying interactions between retinal vascular, structural, and functional changes could enhance knowledge of OIR pathogenesis and potential therapies.

Influence of socio-economic status and educational achievement on cataract formation in a rural community in Imo State, South-Eastern Nigeria

Abstract Purpose: Cataract is a leading cause of visual impairment globally. This study explored medical, behavioral, and socioeconomic factors associated with cataract development in a rural community in Imo State, Nigeria. Methods: A case-control study was done on 61 patients above 40 years old from a medical outreach program to determine the presence of cataract and its risk factors. Results: Of 54 complete records, 52% had cataracts (while 48% had no cataracts). There were no significant differences in co-morbidities such as ocular allergy (OR 0.98, 95% CI: 0.36–2.69), refractive error (OR 1.46, 95% CI: 0.61–3.50), hypertension (OR 0.66, 95% CI: 0.24–1.89), or arthritis (OR 0.90, 95% CI: 0.33–2.43) between people with or without cataract. The no cataract group had a higher educational level (p = 0.01) and socio-economic score (SES, 20.9 ± 2.9 vs. 18.8 ± 3.0, p = 0.01). Both groups obtained medications without a prescription (OR 0.95, 95% CI: 0.40–2.28), and had equivalent sun exposure (3.4 ± 2.9 vs. 3.9 ± 2.2 hours, p = 0.31), use of multivitamins (p = 0.80), sunglasses (p = 0.32), and hats (p = 0.83). Conclusion: Poor knowledge and use of cataract risk reducers in the community contributed to development of cataracts, regardless of socioeconomic status.