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Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity.

ABSTRACT: BACKGROUND:The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization. METHODS:Thirty-one preterm infants undergoing routine ROP screening with written informed consent for research imaging were enrolled in this prospective observational study. We imaged the macula and temporal periphery of preterm infants using a handheld OCT system (Envisu 2300 or handheld swept-source research system). The scans obtained were segmented and, using enhanced ray casting, were converted to 3D volumes to which color filter was applied. RESULTS:Using colorized 3D visualization, we defined extraretinal neovascular structures as buds, bridging networks, and placoid lesions. We could longitudinally follow progression and regression of extraretinal neovascularization in stage 3 ROP after treatment in one infant over 12 weeks and document the appearance of early buds, and formation of florid neovascularization. From stages 2 to 3 ROP, we observed progression from sessile buds to a complex plaque that corresponded to stage 3 ROP on clinical examination. We demonstrated regression of neovascular complexes to small pre-retinal tufts after treatment with anti-VEGF. CONCLUSIONS:The extension of OCT processing to include surface flattening and colorization that further improved structural analysis rendered better understanding of extraretinal tissue. Our ability to image similar areas in the same infant over multiple visits enabled us to study the evolution of these structural components and follow pathological vascular events longitudinally in development and regression after treatment. These methods can be applied to further study which are likely contribute to our understanding of the pathophysiology of neovascularization in ROP.

SUBMITTER: Mangalesh S

PROVIDER: S-EPMC6698900 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity.

Mangalesh Shwetha S Bleicher Isaac D ID Chen Xi X Viehland Christian C LaRocca Francesco F Izatt Joseph A JA Freedman Sharon F SF Hartnett M Elizabeth ME Toth Cynthia A CA

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 20190221 4

<h4>Background</h4>The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization.<h4>Methods</h4>Thirty-one preterm infants undergoing routine ROP screening with written informed cons ...[more]

PMID: 30790072

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Project description:PurposeTo study vascular features detected with spectral domain optical coherence tomography (SD-OCT) in subjects undergoing retinopathy of prematurity (ROP) screening.DesignCross-sectional study.Participants and controlsFifty-seven premature neonates, 10 with plus disease in at least 1 eye and 47 without plus disease.MethodsBedside noncontact SD-OCT imaging was performed after obtaining parental consent on 97 consecutive infants between January 2009 and September 2012. Fifty-seven subjects (31-49 weeks' post-menstrual age) who had an SD-OCT scan in at least 1 eye showing the edge of the optic nerve and at least 1 major retinal vascular arcade were included. One eye per subject was randomly selected for analysis. Two masked graders evaluated scans for (1) retinal vessel elevation, (2) scalloped retinal layers, (3) hyporeflective vessels, and (4) retinal spaces. To coalesce the weight of these features, a Vascular Abnormality Score by OCT (VASO) was created. For quantitative assessment of vessel elevation, retinal surface maps were created.Main outcome measuresPrevalence of SD-OCT vascular abnormalities, the VASO, intergrader agreement, and presence of elevation on surface maps.ResultsFrom among 67 SD-OCT characteristics that were recorded, the most common characteristics found were vessel elevation (44%), hyporeflective vessels (40%), scalloped layers (22%), and retinal spaces (11%). Features significantly associated with plus disease were vessel elevation (P = 0.01), hyporeflective vessels (P = 0.04), and scalloped retinal layers (P = 0.006). Intragrader agreement was between 74% and 90% for all features. The VASO was significantly higher in subjects with plus disease (P = 0.0013). On 3-dimensional SD-OCT volumes, eyes with plus disease had greater retinal surface elevation that more often matched en face retinal vascular patterns.ConclusionsWe present a novel 3-dimensional analysis of vascular and perivascular abnormalities identified in SD-OCT images of eyes with ROP. The SD-OCT characteristics that are more common in eyes with plus disease provide the first in vivo demonstration of the effects of vascular dilation and tortuosity on perivascular tissue. The VASO and surface maps also delineate the severity of vascular pathology in plus disease. Further studies evaluating these findings in eyes with pre-plus versus normal posterior pole vessels may determine the usefulness of SD-OCT in the early detection of vascular abnormalities in ROP.

Project description:TopicRetinopathy of prematurity (ROP) is a proliferative retinal vascular disease in premature infants, and is a major cause of childhood blindness worldwide. In addition to known clinical risk factors such as low birth weight and gestational age, there is a growing body of evidence supporting a genetic basis for ROP.Clinical relevanceWhile comorbidities and environmental factors have been identified as contributing to ROP outcomes in premature infants, most notably gestational age and oxygen, some infants progress to severe disease despite absence of these clinical risk factors. The contribution of genetic factors may explain these differences and allow better detection and treatment of infants at risk for severe ROP.MethodsTo comprehensively review genetic factors that potentially contribute to the development and severity of ROP, we conducted a literature search focusing on the genetic basis for ROP. Terms related to other heritable retinal vascular diseases like "familial exudative vitreoretinopathy", as well as to genes implicated in animal models of ROP, were also used to capture research in diseases with similar pathogenesis to ROP in humans with known genetic components.ResultsContributions across several genetic domains are described including vascular endothelial growth factor, the Wnt signaling pathway, insulin-like growth factor 1, inflammatory mediators, and brain-derived neurotrophic factor.ConclusionsMost candidate gene studies of ROP have limitations such as inability to replicate results, conflicting results from various studies, small sample size, and differences in clinical characterization. Additional difficulty arises in separating the contribution of genetic factors like Wnt signaling to ROP and prematurity. Although studies have implicated involvement of multiple signaling pathways in ROP, the genetics of ROP have not been clearly elucidated. Next-generation sequencing and genome-wide association studies have potential to expand future understanding of underlying genetic risk factors and pathophysiology of ROP.

Project description:IMPORTANCE:Detection of treatment-requiring retinopathy of prematurity (ROP) involves serial eye examinations. An ROP prediction model using predictive factors could identify high-risk infants and reduce required eye examinations. OBJECTIVE:To determine predictive factors for the development of referral-warranted (RW) ROP. DESIGN, SETTING, AND PARTICIPANTS:This multicenter observational cohort study included secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. Infants included in the study had a birth weight (BW) of less than 1251 g. EXPOSURES:Serial ROP examinations of premature infants who had 2 or more ROP examinations. MAIN OUTCOMES AND MEASURES:Incidence of RW-ROP (defined as the presence of plus disease, zone I ROP, or ROP stage 3 or greater in either eye) and associations with predictive factors. RESULTS:Among 979 infants without RW-ROP at first study-related eye examination (median postmenstrual age, 33 weeks; range, 29-40 weeks) who underwent at least 2 eye examinations, 149 (15.2%) developed RW-ROP. In a multivariate model, significant predictors for RW-ROP were male sex (odds ratio [OR], 1.80; 95% CI, 1.13-2.86 vs female), nonblack race (OR, 2.76; 95% CI, 1.50-5.08 for white vs black race and OR, 4.81; 95% CI, 2.19-10.6 for other vs black race), low BW (OR, 5.16; 95% CI, 1.12-7.20 for ?500 g vs >1100 g), younger gestational age (OR, 9.79; 95% CI, 3.49-27.5 for ?24 weeks vs ?28 weeks), number of quadrants with preplus disease (OR, 7.12; 95% CI, 2.53-20.1 for 1-2 quadrants and OR, 18.4; 95% CI, 4.28-79.4 for 3-4 quadrants vs no preplus disease), stage 2 ROP (OR, 4.13; 95% CI, 2.13-8.00 vs no ROP), the presence of retinal hemorrhage (OR, 4.36; 95% CI, 1.57-12.1 vs absence), the need for respiratory support (OR, 4.99; 95% CI, 1.89-13.2 for the need for controlled mechanical ventilator; OR, 11.0; 95% CI, 2.26-53.8 for the need for high-frequency oscillatory ventilation vs no respiratory support), and slow weight gain (OR, 2.44; 95% CI, 1.22-4.89 for weight gain ?12 g/d vs >18 g/d). These characteristics predicted the development of RW-ROP significantly better than BW and gestational age (area under receiver operating characteristic curve, 0.88 vs 0.78; P?<?.001). CONCLUSIONS AND RELEVANCE:When controlling for very low BW and prematurity, the presence of preplus disease, stage 2 ROP, retinal hemorrhage, and the need for ventilation at time of first study-related eye examination were strong independent predictors for RW-ROP. These predictors may help identify infants in need of timely eye examinations.

Dataset Information

Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity.

Publications

Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity.

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