ABSTRACT
PURPOSE: Retinopathy of prematurity (ROP) is considered a disease of the inner retina; however, there is increasing evidence that demonstrates choroidal vasculature loss in ROP, leading to degeneration of outer retinal function and visual deterioration. Central choroidal thinning is noted in children with history of ROP using optical coherence tomography imaging. This study characterizes the presence and persistence of choroidal loss angiographically in eyes of infants treated with intravitreal bevacizumab (IVB) for stage 3 ROP. METHODS: The fluorescein angiography (FA) images of 62 eyes of 31 infants treated with IVB monotherapy were retrospectively reviewed. The eyes with good quality early-, mid-, and late-phase imaging were included in this study. The presence of choroidal hypofluoresence involving the central and or peripheral retina was noted. In infants with multiple FAs, serial FAs were analyzed for persistence of choroidal hypofluorescence. RESULTS: The mean age and birth weight of infants was 24.4 weeks post-menstrual age and 683 g, respectively. All infants received IVB monotherapy. Twenty-four of 62 angiography images of sufficient quality reviewed showed the presence of choroidal hypofluorescence involving central and peripheral lobular loss in the early phase and its persistence into mid- and late phases. Twelve eyes demonstrated persistent choroidal loss on sequential FA until 3 years chronological age. CONCLUSIONS: The study demonstrates the presence of choroidal vascular loss angiographically both central and peripheral fundus in infants with ROP. It highlights the critical role of choroidal involution in outer retinal function that could affect visual outcomes.
Subject(s)
Retinopathy of Prematurity , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Fluorescein Angiography/methods , Gestational Age , Humans , Infant , Infant, Newborn , Intravitreal Injections , Laser Coagulation , Retinopathy of Prematurity/diagnosis , Retinopathy of Prematurity/drug therapy , Retrospective StudiesABSTRACT
INTRODUCTION: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. OBJECTIVE: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. METHODS: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. RESULTS: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. CONCLUSIONS: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.
Subject(s)
Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retina/physiopathology , Retinopathy of Prematurity/drug therapy , Visual Acuity , Angiogenesis Inhibitors/administration & dosage , Animals , Disease Models, Animal , Intravitreal Injections , Mice , Mice, Inbred C57BL , Oxygen/toxicity , Retina/drug effects , Retinopathy of Prematurity/chemically induced , Retinopathy of Prematurity/physiopathology , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
BACKGROUND: Persons with bipolar disorder represent a high-risk group for obesity, but little is known about the time course by which weight gain occurs in bipolar disorder. METHODS: We prospectively studied changes in fat distribution using dual-energy x-ray absorptiometry in relationship to medication exposure and mood symptom burden in 36 participants with bipolar disorder. We assessed the relationship between prior medication exposure and course of illness with adiposity measures at baseline (N = 36) and at 6-month follow-up (N = 22). RESULTS: At baseline, greater adiposity was associated with advanced age and female sex, not retrospectively assessed symptom course or medication exposure (past 2 years). Over 6 months of prospective follow-up, participants developed greater adiposity (fat mass index +0.82 kg/m(²), P = .007; visceral fat area +8.6 cm(²), P = .02; total percent fat +1.6%, P = .02). Manic symptomatology, not antipsychotic exposure, was related to the increased adiposity. CONCLUSIONS: Acute exacerbations of mood disorders appear to represent high-risk periods for adipose deposition. Obesity prevention efforts may be necessary during acute exacerbations.
