Retinopathy of prematurity detection: a retrospective quality improvement project before-after implementation of retinal digital imaging for screening.

Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001). CONCLUSION: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection. WHAT IS KNOWN: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging. WHAT IS NEW: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.

Assistive Framework for Automatic Detection of All the Zones in Retinopathy of Prematurity Using Deep Learning.

Retinopathy of prematurity (ROP) is a potentially blinding disorder seen in low birth weight preterm infants. In India, the burden of ROP is high, with nearly 200,000 premature infants at risk. Early detection through screening and treatment can prevent this blindness. The automatic screening systems developed so far can detect "severe ROP" or "plus disease," but this information does not help schedule follow-up. Identifying vascularized retinal zones and detecting the ROP stage is essential for follow-up or discharge from screening. There is no automatic system to assist these crucial decisions to the best of the authors' knowledge. The low contrast of images, incompletely developed vessels, macular structure, and lack of public data sets are a few challenges in creating such a system. In this paper, a novel method using an ensemble of "U-Network" and "Circle Hough Transform" is developed to detect zones I, II, and III from retinal images in which macula is not developed. The model developed is generic and trained on mixed images of different sizes. It detects zones in images of variable sizes captured by two different imaging systems with an accuracy of 98%. All images of the test set (including the low-quality images) are considered. The time taken for training was only 14 min, and a single image was tested in 30 ms. The present study can help medical experts interpret retinal vascular status correctly and reduce subjective variation in diagnosis.

Long-term evaluation of retinal morphology and function in a mouse model of oxygen-induced retinopathy.

Purpose: Retinopathy of prematurity (ROP) is a condition of aberrant retinal vascularization in premature infants in response to high levels of oxygen used for critical care that can potentially cause blindness. Although therapies to mitigate vascular abnormalities are being evaluated, functional deficits often remain in patients with treated or regressed ROP. This study investigated long-term outcomes of hyperoxia on retinal morphology and function using a mouse model of oxygen-induced ischemic retinopathy (OIR). Methods: Twenty-two mice were exposed to 77% oxygen to induce OIR, while 23 age-matched control mice were raised in room air (RA). In vivo fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and focal electroretinography (fERG) were performed at P19, P24, P32, and P47, followed by histological assessments of retinal morphology, gliosis, microglia activation, and apoptosis. Results: FA in OIR mice showed capillary attrition despite peripheral revascularization. Inner retina thinning was detected with SD-OCT; outer and inner retinal dysfunction were demonstrated with fERG. Histology of the OIR mice exhibited a thin, disorganized structure. Immunohistochemistry showed increased gliosis, microglial activation, and apoptosis with increasing age from P19 to P47. The synapses between rod photoreceptor cells and rod bipolar cells were ectopically localized in the OIR mice. Conclusions: We demonstrated histological evidence of persistent ectopic synapses, prolonged cellular apoptosis, and gliosis in the OIR retina that corresponded with long-term in vivo evidence of capillary attrition, inner retinal thinning, and dysfunction despite full peripheral revascularization. Further studies on the mechanisms underlying these persistent phenotypes could enhance our understanding of ROP pathogenesis and lead to new therapeutic targets to preserve visual function in premature infants.

Comparison of Nd:YAG laser (532 nm green) vs diode laser (810 nm) photocoagulation in the treatment of retinopathy of prematurity: an evaluation in terms of complications.

PURPOSE: To compare the anterior and posterior segment complications of diode (810 nm) laser photocoagulation (LPC) and Nd:YAG (532 nm green) LPC in the treatment of retinopathy of prematurity (ROP). PATIENTS AND METHODS: The 84 eyes of 43 patients treated with diode LPC (group 1) and 58 eyes of 31 patients treated with Nd:YAG LPC (group 2) for ROP in our clinic were enrolled in the study. Medical records of all patients were investigated retrospectively. The patients in each group were examined in terms of birth weights, gestational weeks, stage of retinopathy, number of lasers pots, laser parameters, and anterior and posterior complications of LPC. RESULTS: The mean birth weeks of group 1 patients were postmenstrual 27.7 ± 2.5 (23-33), while the mean birth weights were 1006.0 ± 334.5 (540-1980) grams. The mean birth weeks of group 2 patients were postmenstrual 27.4 ± 2.6 (23-33), while the mean birth weights were 1073.8 ± 329.2 (480-1720) grams. The mean numbers of laser spots were 1036.0 ± 515.2 (430-2410) in group 1 per eye, while the mean numbers of laser spots were 1085.4 ± 526.0 (445-2530) in group 2 per eye (p ≥ 0.05). Additional laser application was performed in four eyes (4.8%) in group 1 and four eyes (6.9%) in group 2. Four eyes (4.8%) treated with diode LPC and one eye (1.7%) treated with Nd:YAG laser developed retinal detachment. Two eyes of a patient (3.4%) applied Nd:YAG LPC developed cataract. CONCLUSION: Cataract may develop when Nd:YAG laser is used; however, posterior segment complications may be more likely to appear with the use of diode laser in these cases.

Automated Detection and Classification of Telemedical Retinopathy of Prematurity Images.

Background: Retinopathy of prematurity (ROP) is a retinal disorder of low birth weight infants and it is the leading cause of childhood blindness. The capability of wide field digital imaging systems to capture the clinical features of ROP has greatly helped the physicians to assess the severity of ROP and prevent childhood blindness due to ROP. Currently there is a lack of automated systems to assess the severity of ROP to assist the ROP specialist to make treatment decision. Objective: To present an automated detection and classification approach to assess the severity of ROP using wide field telemedical images. Materials and Methods: A total of 160 telemedical ROP (tele-ROP) images were collected out, of which 36 images were Normal, 79 images were Stage 2, and 45 images were Stage 3. Hessian analysis and support vector machine (SVM) classifier have been used to detect and classify the severity of ROP from tele-ROP images. Results: Classified the Normal, Stage 2, and Stage 3 images using SVM. Achieved accuracy of 91.8%, sensitivity of 90.37%, specificity of 94.65%, false positive rate of 5.35%, and false negative rate of 9.63%. Conclusions: The automated approach of detecting and classifying ROP would support pediatric ophthalmologists for early treatment decisions with optimal care.

[Fluorescence Angiography-assisted Management of Recurrences in Aggressive Posterior Retinopathy of Prematurity (APROP) after Intravitreal Monotherapy with 0.312 mg Bevacizumab]. / Fluoreszenzangiografieassistiertes Management von Rezidiven bei aggressiver posteriorer Frühgeborenenretinopathie (APROP) nach intravitrealer Monotherapie mit 0,312 mg Bevacizumab.

BACKGROUND: In cases of aggressive posterior retinopathy of prematurity (APROP), recurrences can occur after intravitreal injection of bevacizumab (IVB), in spite of successful treatment of the acute stage. Therefore, long-term examinations in extremely premature patients are needed. We defined recurrences as a relapse of plus disease and leakage (with or without proliferation) at the vascularisation border, but also anterior and posterior to it. METHODS: RetCam wide-field colour images and fluorescein angiography were performed before the first IVB (0.312 mg bevacizumab in 0.025 ml per eye), before each further therapy, i.e. additional intravitreal injection, laser- or cryocoagulation or pars-plana vitrectomy, and at the end of the therapy. We analysed the images of 18 eyes with APROP of 9 extreme premature patients treated between 08/2007 and 12/2017 (GA 21 - 27 weeks, BW 430 - 890 g). RESULTS: Long-term therapeutic success was achieved in only 4 eyes/2 children (22%) with one single injection. In 2 eyes/2 children (11%), a second and third injection was given within 2 weeks because of an insufficient therapeutic effect. Up to 3 injections together with laser coagulation were needed in 12 eyes/6 children (67%), in order to achieve complete resolution of ROP activity. In 6 eyes/2 children (33%), resolution of leakage at the original vascularisation border was achieved only with further laser coagulation. In one single eye, retinal detachment occurred after unsuccessful retinal surgery. Before IVB, fluorescein angiography disclosed leakage due to proliferation in most of the patients (12 eyes/6 children). In recurrences after IVB, a posterior shift of the leakage site was found (14 eyes/4 children), whereas after laser photocoagulation proliferative changes were also detected anterior to the vascularisation border (5 eyes/3 children). Treatment was indicated based on angiographic findings in 14 eyes/4 children where wide-field colour images did not show plus disease or proliferation. CONCLUSIONS: Intravitreal injection of 0.312 mg bevacizumab has been shown to be an effective therapy for the acute stage of APROP. Long-term success required consequent monitoring and treatment of APROP recurrences. Fluorescein angiography was particularly useful to detect recurrences that were not evident in wide-field colour images.

Relationship between Retinal Thickness Profiles and Visual Outcomes in Young Adults Born Extremely Preterm: The EPICure@19 Study.

PURPOSE: To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). DESIGN: Prospective observational study with 19 years of follow-up. PARTICIPANTS: A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy or laser ablation for ROP. METHODS: Subjects underwent eye examinations including best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. MAIN OUTCOME MEASURES: Correlation between retinal sublayer thickness and BCVA. RESULTS: Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P < 0.001), but outer retinal layer thickness was not (r = -0.01, P = 0.80). Multivariate regression indicated ganglion cell layer thickness was a significant independent predictor of BCVA. CONCLUSIONS: Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

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

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.

Efficacy of intravitreal aflibercept monotherapy in retinopathy of prematurity evaluated by periodic fluorescence angiography and optical coherence tomography.

PURPOSE: To evaluate the efficacy of intravitreal aflibercept (IVA) in vascular and macular maturation in neonates with type 1 retinopathy of prematurity (ROP) and aggressive posterior retinopathy of prematurity (APROP). MATERIALS AND METHODS: Thirty-six eyes of 18 patients with type 1 ROP or APROP in zone I or posterior zone II were enrolled in our study. At baseline, only fluorescein angiography (FA) was performed. After IVA injection, both FA and optical coherence tomography (OCT) were performed after 6.8 ± 0.8 (range 6-8) and 19 ± 0.9 (range 18-20) weeks to follow vascular and macular changes. RESULTS: Both diffuse flat neovascularization with leakage and abnormal vascular branching at the small arteriolar level were detected in all eyes (100%) at baseline FA. Regression of the disease was observed in 34 eyes (94.4%) in the first week with binocular indirect ophthalmoscopy. Early unresponsiveness in remaining two eyes of an infant required an IVA re-treatment. Late reactivation was detected only in 19.4% of eyes, none of which required treatment during 12 months of follow-up. The most common feature after IVA injection was abnormal branching at capillary level, which was noted in 100% in the first post-injection FA and 50.0% of all eyes in the second FA. Meanwhile, the end limit of vascularization was observed in zone III in 83.3% of eyes. No vascular abnormality was also detected in 27.3% of eyes. The OCT examination at a mean postmenstrual age of 43.4 weeks revealed cystoid macular changes in four eyes of two infants (11.1%), normal foveal contour in 30 eyes of 15 infants (83.3%) and matured ellipsoid zone at the foveal center in 28 eyes of 14 infants (77.8%). Macular maturation was complete in all eyes in the last OCT analyses. CONCLUSION: Intravitreal aflibercept monotherapy has been an effective treatment in type I ROP and APROP with much lower early and late re-treatment rates because of early unresponsiveness and late reactivation, respectively. In most of the eyes, rapid vascular outgrowth beyond zone III together with normal macular maturation was observed more precisely by periodic FA and OCT.

Severe retinopathy of prematurity is associated with reduced cerebellar and brainstem volumes at term and neurodevelopmental deficits at 2 years.

BackgroundTo evaluate the association between severe retinopathy of prematurity (ROP), measures of brain morphology at term-equivalent age (TEA), and neurodevelopmental outcome.MethodsEighteen infants with severe ROP (median gestational age (GA) 25.3 (range 24.6-25.9 weeks) were included in this retrospective case-control study. Each infant was matched to two extremely preterm control infants (n=36) by GA, birth weight, sex, and brain injury. T2-weighted images were obtained on a 3 T magnetic resonance imaging (MRI) at TEA. Brain volumes were computed using an automatic segmentation method. In addition, cortical folding metrics were extracted. Neurodevelopment was formally assessed at the ages of 15 and 24 months.ResultsInfants with severe ROP had smaller cerebellar volumes (21.4±3.2 vs. 23.1±2.6 ml; P=0.04) and brainstem volumes (5.4±0.5 ml vs. 5.8±0.5 ml; P=0.01) compared with matched control infants. Furthermore, ROP patients showed a significantly lower development quotient (Griffiths Mental Development Scales) at the age of 15 months (93±15 vs. 102±10; P=0.01) and lower fine motor scores (10±3 vs. 12±2; P=0.02) on Bayley Scales (Third Edition) at the age of 24 months.ConclusionSevere ROP was associated with smaller volumes of the cerebellum and brainstem and with poorer early neurodevelopmental outcome. Follow-up through childhood is needed to evaluate the long-term consequences of our findings.

PROPHYLACTIC PERIPHERAL LASER AND FLUORESCEIN ANGIOGRAPHY AFTER BEVACIZUMAB FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To report reactivation rate after bevacizumab treatment for retinopathy of prematurity (ROP) in eyes with classic ROP (CROP) versus aggressive posterior ROP (APROP) and to report peripheral fluorescein angiography findings in these eyes. METHODS: Retrospective chart review was conducted on consecutive infants treated with bevacizumab for ROP, followed by fluorescein angiography and prophylactic laser to persistent avascular retina. RESULTS: Sixty-four eyes of 33 patients were included. Mean gestational age was 25 weeks with mean birth weight of 674 g. Mean follow-up was 125 weeks post-menstrual age (PMA). Reactivation requiring treatment after initial bevacizumab was more common in eyes with APROP (8/16) than with CROP (2/48; P < 0.0001). At mean 73 weeks PMA, eyes with APROP had more avascular retina (mean 4.4 disk diameters vs. 2.6 disk diameters; P = 0.0004) and higher percentage of leakage (11/11 eyes vs. 22/38 eyes; P = 0.01) on fluorescein angiography than in eyes with CROP. Unfavorable outcome occurred in 1 of 16 eyes with APROP and in no eyes with CROP. No eye that underwent prophylactic laser after bevacizumab had a poor structural outcome. CONCLUSION: In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.

HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING THROUGH THE UNDILATED PUPIL IN INFANTS BORN PRETERM OR WITH HYPOXIC INJURY OR HYDROCEPHALUS.

PURPOSE: The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities. METHODS: Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities. RESULTS: The authors obtained images through an undilated pupil of 11 infants/children over 28 eye imaging sessions, 27 at the bedside without sedation, and one under anesthesia. Infants had retinopathy of prematurity (n = 8), hypoxic ischemic encephalopathy (n = 2), or obstructive hydrocephalus (n = 1 child). Pupil sizes ranged from 1.0 mm to 3.5 mm. The authors captured fovea and optic nerve scans in 25/28 eye imaging sessions, with scans of adequate quality to discern prespecified foveal and optic nerve morphology, and of the 25 sessions, the choroidal-scleral junction was visible in all but 6 sessions. CONCLUSION: Undilated, handheld SDOCT imaging is a potential alternative method to evaluate the retina and optic nerve in patients with relative contraindication to pharmacological pupil dilation. This approach will enable the study of the eye-brain connection and ocular manifestations of neurologic diseases.

The macular findings on spectral-domain optical coherence tomography in premature infants with or without retinopathy of prematurity.

The purpose of the study was to present spectral-domain optical coherence tomography (OCT) findings in premature infants with or without mild-to-severe retinopathy of prematurity (ROP). Seventy-two infants born <37 weeks of gestation were analyzed, prospectively. Group 1 (n = 18) included infants without ROP. Infants with stage 1, 2, or 3 ROP without indication for treatment formed the second group (n = 15). Group 3 (n = 21) included threshold cases, who would receive laser photocoagulation (LPC) after OCT examinations. Group 4 (n = 18) had already received LPC. The mean central foveal thickness (CFT) (µm) in right eyes was 194.27 ± 19.93, 207.67 ± 25.44, 224.29 ± 21.42, and 222.00 ± 37.80, for groups 1, 2, 3, and 4, respectively (p = 0.01). The presence of a well-formed foveal pit was documented in 60 % of right and 67 % of left eyes in group 1, while a well-formed foveal pit was observed in 14 % of right and 16 % of left eyes in group 3 (p < 0.05). Cystoid macular edema (CME) was shown in 29 % of right and 21 % of left eyes in group 3 (p < 0.05 for right eyes). CME was observed in two of right and left eyes in group 4. Epiretinal membrane (ERM) was shown in one right eye in group 3, two right and four left eyes in group 4 (p < 0.05 for left eyes). Thicker CFT, CME, and failure of a well-formed foveal pit could be related to the severity of ROP. The development of ERM could be the consequence of LPC.

Ocular blood flow in preterm neonates.

Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.

A fundus image dataset for intelligent retinopathy of prematurity system.

Image-based artificial intelligence (AI) systems stand as the major modality for evaluating ophthalmic conditions. However, most of the currently available AI systems are designed for experimental research using single-central datasets. Most of them fell short of application in real-world clinical settings. In this study, we collected a dataset of 1,099 fundus images in both normal and pathologic eyes from 483 premature infants for intelligent retinopathy of prematurity (ROP) system development and validation. Dataset diversity was visualized with a spatial scatter plot. Image classification was conducted by three annotators. To the best of our knowledge, this is one of the largest fundus datasets on ROP, and we believe it is conducive to the real-world application of AI systems.

Assessing spectral effectiveness in color fundus photography for deep learning classification of retinopathy of prematurity.

Significance: Retinopathy of prematurity (ROP) poses a significant global threat to childhood vision, necessitating effective screening strategies. This study addresses the impact of color channels in fundus imaging on ROP diagnosis, emphasizing the efficacy and safety of utilizing longer wavelengths, such as red or green for enhanced depth information and improved diagnostic capabilities. Aim: This study aims to assess the spectral effectiveness in color fundus photography for the deep learning classification of ROP. Approach: A convolutional neural network end-to-end classifier was utilized for deep learning classification of normal, stage 1, stage 2, and stage 3 ROP fundus images. The classification performances with individual-color-channel inputs, i.e., red, green, and blue, and multi-color-channel fusion architectures, including early-fusion, intermediate-fusion, and late-fusion, were quantitatively compared. Results: For individual-color-channel inputs, similar performance was observed for green channel (88.00% accuracy, 76.00% sensitivity, and 92.00% specificity) and red channel (87.25% accuracy, 74.50% sensitivity, and 91.50% specificity), which is substantially outperforming the blue channel (78.25% accuracy, 56.50% sensitivity, and 85.50% specificity). For multi-color-channel fusion options, the early-fusion and intermediate-fusion architecture showed almost the same performance when compared to the green/red channel input, and they outperformed the late-fusion architecture. Conclusions: This study reveals that the classification of ROP stages can be effectively achieved using either the green or red image alone. This finding enables the exclusion of blue images, acknowledged for their increased susceptibility to light toxicity.

Retinal Image Dataset of Infants and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) represents a vasoproliferative disease, especially in newborns and infants, which can potentially affect and damage the vision. Despite recent advances in neonatal care and medical guidelines, ROP still remains one of the leading causes of worldwide childhood blindness. The paper presents a unique dataset of 6,004 retinal images of 188 newborns, most of whom are premature infants. The dataset is accompanied by the anonymized patients' information from the ROP screening acquired at the University Hospital Ostrava, Czech Republic. Three digital retinal imaging camera systems are used in the study: Clarity RetCam 3, Natus RetCam Envision, and Phoenix ICON. The study is enriched by the software tool ReLeSeT which is aimed at automatic retinal lesion segmentation and extraction from retinal images. Consequently, this tool enables computing geometric and intensity features of retinal lesions. Also, we publish a set of pre-processing tools for feature boosting of retinal lesions and retinal blood vessels for building classification and segmentation models in ROP analysis.

A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity.

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

The long-term influence of perinatal factors on macular morphology and vessel density in preterm children.

BACKGROUND: Increased survival rate of extremely preterm children is associated with a higher risk of retinopathy of prematurity (ROP) and long-term sequelae, which implicate retinal changes. PURPOSE: To assess an influence of perinatal characteristics on morphology and retinal vascularity of the macula in preterm children. METHODS: A cohort of 123 preterm children at the age of 10.5 years (IQR: 8.12-12.77) was prospectively assessed. Optical coherence tomography angiography (OCTA) was performed using RTVueXR Avanti. Foveal thickness, parafoveal thickness, size of foveal avascular zone (FAZ), superficial and deep vessel density, central choroidal thickness (CCT) were analyzed. The associations between OCTA results and perinatal factors, including the presence of ROP and therapy requirements were assessed in preterm children. RESULTS: Significantly smaller FAZ, higher foveal thickness and vessel density were noted in children with ROP, Respiratory Distress Syndrome, Bronchopulmonary Dysplasia, required erythropoietin, transfusion or steroids. Foveal thickness was increased in children with ROP (p < 0.001) and following laser treatment (p < 0.05). Thinner CCT was noted in children with a history of sepsis (p < 0.05) and ROP required treatment (p < 0.05). Pregnancy bleeding was associated with higher superficial foveal vessel density (p < 0.05) and smaller FAZ (p < 0.05). CONCLUSION: Neonatal factors have a huge impact on retinal development, but the role of prenatal factors should not be neglected in preterm children.