{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:35:26Z","timestamp":1792733726945,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Retinal morphology changes may be associated with prematurity and can lead to visual impairment. Optical coherence tomography angiography may contribute to understanding the pathomechanism of structural and vascular retinal impairment in premature children. The aim of this study was to assess an influence of prematurity, neonatal clinical characteristics, and a history of retinopathy of prematurity (ROP) on the morphology and retinal vascularity of macula in children. Methods: A case\u2013control study of 123 preterm children and 86 full-term children was performed. The age of the subjects was 10.45 years (IQR: 8.12\u201312.77), while the age of the control group was 11.78 years (IQR: 8.81\u201313.79). Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA, angio-OCT) were performed using RTVueXR Avanti (Optovue, Fremont, CA, USA). Ganglion cell complex (GCC), foveal thickness (FT), parafoveal thickness (PFT), size of foveal avascular zone (FAZ) in superficial plexus, superficial capillary vessel density (sVD), deep capillary vessel density (dVD), central choroidal thickness (CCT), and presence of macular hypoplasia were analyzed. The association between OCT\/angio-OCT results and clinical characteristics including the degree of ROP and therapy requirements was assessed in preterm infants. Results: Foveal morphology was affected in preterm children with high incidence of foveal hypoplasia (24.77%). GCC was thinner in preterm children compared to controls: avgGG 93 \u03bcm vs. 100 \u03bcm, p &lt; 0.001. No associations between GCC and gestational age (R = \u22120.085; p = 0.228) and birth weight (R = \u22120.054; p = 0.446) were found. FAZ in preterm group was smaller than in controls (0.13 \u00b1 0.09 vs. 0.22 \u00b1 0.09; p &lt; 0.001). FAZ area correlated with gestational age (R = 0.456; p &lt; 0.001) and birth weight (R = 0.472; p &lt; 0.001). Deep vessel density in the fovea was higher in preterm children than in control group (p &lt; 0.001). PFT was significantly lower in preterm children compared to control group. However, increased thickness in the fovea was noted in preterm children (p &lt; 0.001). FT was inversely correlated with gestational age (R = \u22120.562; p &lt; 0.001) and birth weight (R = \u22120.508, p &lt; 0.001). CCT was lower in preterm children (312 \u03bcm vs. 337.5 \u03bcm, p &lt; 0.001) Parameters of GCC and FT were higher in patients with ROP required treatment compared to patients without ROP and spontaneously regressed retinopathy. FAZ was smaller in patients with retinopathy than in preterm children without ROP. Conclusion: Prematurity has a significant negative impact on GCC, macular morphology, and vascularization. In premature children, decreased FAZ, increased FT, and vessel density were strongly associated with gestational age, birth weight, Apgar score, ROP stage, and treatment requirement. Optical coherence tomography angiography is a useful tool for detecting retinal changes in premature children.<\/jats:p>","DOI":"10.3390\/jcm11051337","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:11:14Z","timestamp":1646079074000},"page":"1337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Morphology and Vessel Density of the Macula in Preterm Children Using Optical Coherence Tomography Angiography"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-2458","authenticated-orcid":false,"given":"Agnieszka","family":"Czeszyk","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Hautz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-371X","authenticated-orcid":false,"given":"Maciej","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Bulsiewicz","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Neonatal Intensive Care, Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-3951","authenticated-orcid":false,"given":"Justyna","family":"Czech-Kowalska","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Neonatal Intensive Care, Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","first-page":"1556","article-title":"Comparison of OCT angiography in children with a history of intravitreal injection of ranibizumab versus laser photocoagulation for retinopathy of prematurity","volume":"104","author":"Zhao","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1097\/IAE.0000000000002301","article-title":"Visual Function and Optical Coherence Tomography Angiography Features in Children Born Preterm","volume":"39","author":"Balasubramanian","year":"2019","journal-title":"Retina"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1097\/IAE.0000000000001471","article-title":"Optical Coherence Tomography Angiography of the Fovea in Children Born Preterm","volume":"37","author":"Falavarjani","year":"2017","journal-title":"Retina"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1001\/archopht.123.7.991","article-title":"The International Classification of Retinopathy of Prematurity Revisited","volume":"123","author":"Gole","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Early Treatment for Retinopathy of Prematurity Cooperative Group (2003). Revised indications for the treatment of retinopathy of prematurity: Results of the early treatment for retinopathy of prematurity randomized trial. Arch. Ophthalmol., 121, 168494. Clinical Trial.","DOI":"10.1001\/archopht.121.12.1684"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1038\/s41433-019-0500-5","article-title":"Foveal abnormalities determined by optical coherence tomography angiography in children with history of retinopathy of prematurity","volume":"33","author":"Takagi","year":"2019","journal-title":"Eye"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/eye.2017.156","article-title":"The inner retinal structures of the eyes of children with a history of retinopathy of prematurity","volume":"32","author":"Lee","year":"2017","journal-title":"Eye"},{"key":"ref_8","first-page":"e222","article-title":"Clinical relevance of retinal structure in children with laser-treated retinopathy of prematurity versus controls\u2014Using optical coherence tomography","volume":"96","author":"Stoica","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1001\/jamaophthalmol.2013.5052","article-title":"Choroidal Thickness in Patients with a History of Retinopathy of Prematurity","volume":"131","author":"Wu","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_10","first-page":"75","article-title":"Structural development of the visual system of man","volume":"3","author":"Garey","year":"1984","journal-title":"Hum. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0042-6989(86)90143-4","article-title":"A qualitative and quantitative analysis of the human fovea during development","volume":"26","author":"Yuodelis","year":"1986","journal-title":"Vis. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0161-6420(84)34247-6","article-title":"The Morphological Development of the Human Fovea","volume":"91","author":"Hendrickson","year":"1984","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ajo.2011.06.017","article-title":"Subfoveal Fluid in Healthy Full-term Newborns Observed by Handheld Spectral-Domain Optical Coherence Tomography","volume":"153","author":"Cabrera","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Go\u0142\u0119biewska, J., Olechowski, A., Wysocka-Mincewicz, M., Odrobina, D., Baszy\u0144ska-Wilk, M., Groszek, A., Szalecki, M., and Hautz, W. (2017). Optical coherence tomography angiography vessel density in children with type 1 diabetes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186479"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1007\/s00417-021-05090-7","article-title":"Optical coherence tomography angiography in preterm-born children with retinopathy of prematurity","volume":"259","author":"Vinekar","year":"2021","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/IAE.0000000000001937","article-title":"Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Children with a History of Treatment-Requiring Retinopathy of Prematurity","volume":"39","author":"Nonobe","year":"2019","journal-title":"Retina"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1161\/HYPERTENSIONAHA.120.16734","article-title":"Remodeling of Retinal Microcirculation is Associated with Subclinical Arterial Injury in Hypertensive Children","volume":"77","author":"Rogowska","year":"2021","journal-title":"Hypertension"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/WNO.0000000000000345","article-title":"Retinal Ganglion Cell Loss Precedes Retinal Nerve Fiber Thinning in Nonarteritic Anterior Ischemic Optic Neuropathy","volume":"36","author":"Akbari","year":"2016","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000478052","article-title":"Ganglion Cell-Inner Plexiform Layer Thickness in Different Glaucoma Stages Measured by Optical Coherence Tomography","volume":"59","author":"Zivkovic","year":"2018","journal-title":"Ophthalmic Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"879","DOI":"10.2147\/OPTH.S3361","article-title":"Hypoxia-ischemia and retinal ganglion cell damage","volume":"2","author":"Kaur","year":"2008","journal-title":"Clin. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/S0140-6736(13)60178-6","article-title":"Retinopathy of prematurity","volume":"382","author":"Smith","year":"2013","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.ajo.2014.12.015","article-title":"Microstructural Changes in the Retina Related to Prematurity","volume":"159","author":"Pueyo","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8340729","DOI":"10.1155\/2019\/8340729","article-title":"The Size of the Foveal Avascular Zone Is Associated with Foveal Thickness and Structure in Premature Children","volume":"2019","author":"Miki","year":"2019","journal-title":"J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/eye.2014.207","article-title":"Choroidal thickness in regressed retinopathy of prematurity","volume":"28","author":"Anderson","year":"2014","journal-title":"Eye"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.1167\/iovs.12-10599","article-title":"Analysis of spectral-domain optical coherence tomography in preterm children: Retinal layer thickness and choroidal thickness profiles","volume":"53","author":"Park","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1001\/archopht.121.4.547","article-title":"Retinal oxygen: Fundamental and clinical aspects","volume":"121","author":"Linsenmeier","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/IAE.0b013e318219e685","article-title":"Critical Period for Foveal Fine Structure in Children with Regressed Retinopathy of Prematurity","volume":"32","author":"Wang","year":"2012","journal-title":"Retina"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S1350-9462(01)00012-X","article-title":"Development of the Primate Retinal Vasculature","volume":"20","author":"Provis","year":"2001","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00417-018-4162-y","article-title":"Foveal microvascular anomalies on optical coherence tomography angiography and the correlation with foveal thickness and visual acuity in retinopathy of prematurity","volume":"257","author":"Chen","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000488368","article-title":"Foveal Depression and Related Factors in Patients with a History of Retinopathy of Prematurity","volume":"240","author":"Miki","year":"2018","journal-title":"Ophthalmologica"},{"key":"ref_31","first-page":"e232","article-title":"Retinal vessel architecture in retinopathy of prematurity and healthy controls using swept-source optical coherence tomography angiography","volume":"99","author":"Eibenberger","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics Committee on Fetus and Newborn (2015). American College of obstetricians and gynecologists committee on obstetric practice. The Apgar Score. Pediatrics, 136, 819\u2013822.","DOI":"10.1542\/peds.2015-2651"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jamapediatrics.2020.1097","article-title":"Association of Intrauterine Growth Restriction and Small for Gestational Age Status with Childhood Cognitive Outcomes: A systematic review and meta-analysis","volume":"174","author":"Sacchi","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1016\/j.ophtha.2009.05.025","article-title":"Detection of Macular Ganglion Cell Loss in Glaucoma by Fourier-Domain Optical Coherence Tomography","volume":"116","author":"Tan","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.ophtha.2011.01.028","article-title":"Structural Grading of Foveal Hypoplasia Using Spectral-Domain Optical Coherence Tomography: A Predictor of Visual Acuity?","volume":"118","author":"Thomas","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1097\/IAE.0000000000000765","article-title":"Image artifacts in optical coherence tomography angiography","volume":"35","author":"Spaide","year":"2015","journal-title":"Retina"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1097\/IAE.0000000000002581","article-title":"Increased foveal ganglion cell and inner plexiform layer thickness in children aged 6.5 years born extremely preterm","volume":"40","author":"Hellgren","year":"2020","journal-title":"Retina"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1136\/bjophthalmol-2012-301612","article-title":"Foveal avascular zone and foveal pit formation after preterm birth","volume":"96","author":"Yanni","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1542\/peds.2004-1309","article-title":"Prenatal Risk Factors for Severe Retinopathy of Prematurity among Very Preterm Infants of the Australian and New Zealand Neonatal Network","volume":"115","author":"Darlow","year":"2005","journal-title":"Pediatrics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.47102\/annals-acadmedsg.V34N2p169","article-title":"Incidence, risk factors of retinopathy of prematurity among very low birth weight infants in Singapore","volume":"34","author":"Shah","year":"2005","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1136\/bjo.2003.027474","article-title":"Threshold retinopathy at threshold of viability: The EpiBel study","volume":"88","author":"Allegaert","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/eye.2017.18","article-title":"Characteristic clinical features associated with aggressive posterior retinopathy of prematurity","volume":"31","author":"Ahn","year":"2017","journal-title":"Eye"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000323764","article-title":"Risk Factors and Outcomes for Retinopathy of Prematurity in Neonatal Infants with a Birth Weight of 1501\u20132000 g in a Chinese Neonatal Unit","volume":"20","author":"Gu","year":"2011","journal-title":"Med Princ. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1097\/IAE.0000000000001458","article-title":"Variability in foveal avascular zone and capillary density using optical coherence tomography angiography machines in healthy eyes","volume":"37","author":"Magrath","year":"2017","journal-title":"Retina"},{"key":"ref_45","first-page":"1217","article-title":"Vascularization of the human fetal retina: Roles (39) of vasculogenesis and angiogenesis","volume":"41","author":"Hughes","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/bjophthalmol-2015-307330","article-title":"Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography","volume":"100","author":"Carpineto","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S0161-6420(99)00732-0","article-title":"A small foveal avascular zone may be an historic mark of prematurity","volume":"106","author":"Satriano","year":"1999","journal-title":"Ophthalmology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ajo.2020.05.025","article-title":"Retinopathy of Prematurity: Evolving Treatment with Anti\u2013Vascular Endothelial Growth Factor","volume":"218","author":"Hartnett","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Celiker, H., and Sahin, O. (2021). Angiographic findings in cases with a history of severe retinopathy of prematurity treated with anti-VEGFs: Follow-up to age 6 years. Int. Ophthalmol., 1\u201321.","DOI":"10.21203\/rs.3.rs-335877\/v1"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10103-011-1021-z","article-title":"Laser treatment for retinopathy of prematurity","volume":"28","author":"Houston","year":"2013","journal-title":"Lasers Med Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:29:17Z","timestamp":1760135357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jcm11051337"],"URL":"https:\/\/doi.org\/10.3390\/jcm11051337","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]}}}