Algorithms for the automatic tracking of the blood vessels network in retinal images acquired by RetCam in newborns

L’obiettivo di questo lavoro di tesi è la realizzazione di una serie di algoritmi capaci di tracciare automaticamente i vasi retinici in immagini acquisite tramite RetCam (field of view=130°) da neonati prematuri. I neonati prematuri rischiano infatti di sviluppare una patologia (Retinopatia del Prematuro) che se non correttamente trattata può portare al distacco retinico e alla cecità. L’analisi del fondo oculare è l’unico modo per determinare la condizione del paziente ma decidere se intervenire o meno in un neonato dovrebbe essere una decisione basata su dati oggettivi e su un protocollo ben definito. Il tracciamento automatico dei vasi retinici in immagini RetCam è un processo complicato data la scarsa qualità delle immagini da elaborare, soprattutto per la trasparenza della retina nei neonati e per il basso contrasto delle immagini, ma rappresenta uno step fondamentale per la successiva valutazione automatica della condizione della retina sotto esame. In questo lavoro sono state considerate 20 immagini, di cui è stato realizzato il tracciamento manuale per determinare la performance del sistema implementato. Fra le 20 immagini ne sono state scelte 6 per allenare un classificatore che , a partire dalle immagini filtrate, distingueva ogni segmento dell’immagine come appartenente o meno alla rete di vasi retinici. il risultato finale è dato dalla combinazione delle 2 classificazioni disponibili per ogni immagine ed è caratterizzato da un’immagine binaria avente i vasi retinici bianchi su sfondo ner

Quantification of Global Tortuosity in Retinal Blood Vessels

Tortuosity is a parameter that indicates the tendency of a blood vessel segment to contain multiple twists and turns. Chronic hemodynamic changes in the body due to diabetes and hypertension will manifest as increased retinal vascular tortuosity, rendering tortuosity as a suitable indicator for diabetic and hypertensive retinopathy. Retinal tortuosity may be evaluated locally on a single segment or globally in the complete vascular network. Global tortuosity quantification consists of automated segmentation and partition of retinal vessel network, local tortuosity measurement, and global tortuosity index derivation from weighted combination of local tortuosity values. This paper proposes several weighting schemes and evaluates their performance when combined with different local tortuosity indexes. We perform rank correlation analysis to find the global tortuosity quantification that is most consistent with the ophthalmologists. Our results show that local tortuosity indexes that are robust to variations in scale and number of sampling points provide the best performance. Furthermore, weighting scheme based on chord length yields better results than the one based on arc length. The combination of Tortuosity Density (TD) local index and Tortuosity Density Global (TDG) weighting scheme provides the highest consistency with ophthalmologists, with the average rank correlation coefficient of 0.98 (p-value < 0.03)

Vitreoretinal biomarkers of retinopathy of prematurity using handheld optical coherence tomography: a review

Retinopathy of prematurity (ROP) is caused by abnormal retinal vascularization in premature infants that has the potential for severe long-term vision impairment. Recent advancements in handheld optical coherence tomography (OCT) have enabled noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. The use of handheld OCT devices in the diagnosis of ROP in premature infants has furthered our understanding of disease state and progression. This review discusses the known and novel biomarkers of ROP severity in premature infants identified through handheld OCT and potential for future directions

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial

BACKGROUND: Despite increasing worldwide use of anti-vascular endothelial growth factor agents for treatment of retinopathy of prematurity (ROP), there are few data on their ocular efficacy, the appropriate drug and dose, the need for retreatment, and the possibility of long-term systemic effects. We evaluated the efficacy and safety of intravitreal ranibizumab compared with laser therapy in treatment of ROP. METHODS: This randomised, open-label, superiority multicentre, three-arm, parallel group trial was done in 87 neonatal and ophthalmic centres in 26 countries. We screened infants with birthweight less than 1500 g who met criteria for treatment for retinopathy, and randomised patients equally (1:1:1) to receive a single bilateral intravitreal dose of ranibizumab 0·2 mg or ranibizumab 0·1 mg, or laser therapy. Individuals were stratified by disease zone and geographical region using computer interactive response technology. The primary outcome was survival with no active retinopathy, no unfavourable structural outcomes, or need for a different treatment modality at or before 24 weeks (two-sided α=0·05 for superiority of ranibizumab 0·2 mg against laser therapy). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02375971. INTERPRETATION: Between Dec 31, 2015, and June 29, 2017, 225 participants (ranibizumab 0·2 mg n=74, ranibizumab 0·1 mg n=77, laser therapy n=74) were randomly assigned. Seven were withdrawn before treatment (n=1, n=1, n=5, respectively) and 17 did not complete follow-up to 24 weeks, including four deaths in each group. 214 infants were assessed for the primary outcome (n=70, n=76, n=68, respectively). Treatment success occurred in 56 (80%) of 70 infants receiving ranibizumab 0·2 mg compared with 57 (75%) of 76 infants receiving ranibizumab 0·1 mg and 45 (66%) of 68 infants after laser therapy. Using a hierarchical testing strategy, compared with laser therapy the odds ratio (OR) of treatment success following ranibizumab 0·2 mg was 2·19 (95% Cl 0·99-4·82, p=0·051), and following ranibizumab 0·1 mg was 1·57 (95% Cl 0·76-3·26); for ranibizumab 0·2 mg compared with 0·1 mg the OR was 1·35 (95% Cl 0·61-2·98). One infant had an unfavourable structural outcome following ranibizumab 0·2 mg, compared with five following ranibizumab 0·1 mg and seven after laser therapy. Death, serious and non-serious systemic adverse events, and ocular adverse events were evenly distributed between the three groups. FINDINGS: In the treatment of ROP, ranibizumab 0·2 mg might be superior to laser therapy, with fewer unfavourable ocular outcomes than laser therapy and with an acceptable 24-week safety profile. FUNDING: Novartis

The relationship between body growth, retinal blood vessel development and the incidence of retinopathy of prematurity: a clinical and laboratory investigation

The relationship between body growth, retinal blood vessel development and the incidence of retinopathy of prematurity: a clinical and laboratory investigationBACKGROUND: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina in preterm infants and an important cause of childhood blindness. The incidence of ROP has varied over time and across the world as a result of changes in clinical neonatal practice. ROP is a multifactorial disease with low birth weight, low gestational age and exposure to supplemental oxygen being key risk factors. Prenatal and postnatal body growth together with availability of growth factors may also be involved in the pathogenesis. Premature infants undergo eye screening using binocular indirect ophthalmoscopy (BIO) or wide-field digital retinal imaging (WFDRI) in order to identify those infants with sight-threatening disease that require treatment with laser photocoagulation. Eye screening is a painful and distressing procedure for infants.AIMS: (i) To report the trends in incidence of ROP within Lothian, Scotland (ii) To report the incidence of ROP in small-for-gestational (SGA) infants (iii) To study retinal vascular development in growth-restricted rat pups (iv) To carry out a prospective randomised study comparing the diagnostic accuracy of WFDRI with BIO for ROP eye examinations (v) To compare the pain experienced by infants undergoing WFDRI and BIOMETHODS: Data from eye screening examinations within Lothian between 1990 and 2004 were analysed and epidemiological data were obtained from the Scottish Health Service. Dams of rat pups were fed either a 'normal' (18%) or 'low' (9%) protein diet. Dams and pups were exposed to either room air or a fluctuating oxygen profile for 14 days. Retinas were dissected and blood vessels were stained using immunohistochemistry. The extent of vascular development was measured and compared between animal groups. Serum was collected from pups and levels of insulin-like growth factor-1 (IGF-1) were measured using an enzyme-linked immunosorbent assay. Infants from Edinburgh Neonatal Unit undergoing routine ROP screening were recruited and screened by both WFDRI and BIO in random order. The sensitivity and specificity of WFDRI compared to BIO was calculated. The pain experienced by infants was scored using the Premature Infant Pain Profile (PIPP) and compared between the two techniques.RESULTS: There has been an increase in survival of preterm infants, a reduction in the incidence of any degree of ROP, severe ROP and a marked reduction in treatment for ROP in Lothian from 1990-2004. The prevalence of ROP and severe ROP were higher in SGA infants than their appropriately sized peers. Pups of dams fed the 9% protein diet were born growth restricted. The growth restricted rat pups had significantly larger retinal avascular areas and lower serum IGF-1 levels than 'normal' sized pups. The sensitivity of WFDRI in detecting any ROP, stage 3 ROP and plus disease was 60%, 57% and 80% respectively with a specificity of 91%, 98% and 98% respectively. ROP screening using WFDRI and BIO was painful but the pain experienced by infants was similar for both techniques (WFDRI PIPP score 15.0, BIO PIPP score 15.2).CONCLUSIONS: Advances in obstetric and neonatal care within the developed world over the last two decades are likely responsible for the increased survival of premature infants and the overall decreasing incidence of ROP seen in Lothian. Body growth and IGF-1 are important in the pathogenesis of ROP. Further work is required to identify a mechanism for this association and clinical trials of nutritional therapies are needed. WFDRI is a useful examination technique for ROP eye screening but has some technical limitations which need to be improved. Further work is required to implement adequate analgesia regimes for ROP screening

Estimation of Gestational Age via Image Analysis of Anterior Lens Capsule Vascularity in Preterm Infants: A Pilot Study

Introduction: Anterior lens capsule vascularity (ALCV) is resorbed in the developing fetus from 27 to 35 weeks gestation. In this pilot study, we evaluated the feasibility and validity of combining smartphone ophthalmoscope videos of ALCV and image analysis for gestational age estimation.Methods: ALCV videos were captured longitudinally in preterm neonates from delivery using a PanOptic® Ophthalmoscope with an iExaminer® adapter (Welch-Allyn). ALCV video frames were manually selected and quantified using semi-automatic image analysis. A predictive model based on ALCV features was compared to gold-standard ultrasound gestational age estimates.Results: A total of 64 image-capture sessions were carried out in 24 neonates. Ultrasound-estimated gestational age and ALCV-predicted gestational age estimates indicate that the two methods are similar (r = 0.78, p < 0.0001). ALCV estimates of gestational age were within 0.11 ± 1.3 weeks of ultrasound estimates. In the final model, gestational age was predicted within ± 1 week for 54% and within ± 2 weeks for 86% of the measures.Conclusions: This novel application of smartphone ophthalmoscopy and ALCV image analysis may provide a safe, accurate and non-invasive technology to estimate postnatal gestational age, especially in low income countries where gestational age may not be known at birth