{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:17:23Z","timestamp":1789762643116,"version":"4.0.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum M\u00fcnster"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4\u00a0mm diameter and a circle of 6\u00a0mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36\u2009\u00b1\u20098.39\u00a0mm<jats:sup>2<\/jats:sup> at baseline to 37.77\u2009\u00b1\u20099.03\u00a0mm<jats:sup>2<\/jats:sup> at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p\u2009&lt;\u20090.001; ring: p\u2009&lt;\u20090.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p\u2009&lt;\u20090.001; ring: p\u2009&lt;\u20090.001). Evaluation of CC parameters suggested significant group\u2009\u00d7\u2009time interaction effects for CC FD (p\u2009=\u20090.04) and mean intensity signal (p\u2009=\u20090.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5\u00a0years in both RPD-affected and RPD-unaffected macular areas.<\/jats:p>","DOI":"10.1038\/s41598-021-97771-w","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T10:03:16Z","timestamp":1631613796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Longitudinal choriocapillaris changes in the presence of reticular pseudodrusen"],"prefix":"10.1038","volume":"11","author":[{"given":"Christoph R.","family":"Clemens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jost L.","family":"Lauermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Eter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Alten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"97771_CR1","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1016\/j.ophtha.2013.12.034","volume":"121","author":"RP Finger","year":"2014","unstructured":"Finger, R. P. et al. Reticular pseudodrusen: A risk factor for geographic atrophy in fellow eyes of individuals with unilateral choroidal neovascularization. Ophthalmology 121, 1252\u20131256 (2014).","journal-title":"Ophthalmology"},{"key":"97771_CR2","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1001\/jamaophthalmol.2020.0266","volume":"138","author":"C Dutheil","year":"2020","unstructured":"Dutheil, C. et al. Incidence and risk factors of reticular pseudodrusen using multimodal imaging. JAMA Ophthalmol. 138, 467\u2013477 (2020).","journal-title":"JAMA Ophthalmol."},{"key":"97771_CR3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.ophtha.2009.07.014","volume":"117","author":"SA Zweifel","year":"2010","unstructured":"Zweifel, S. A., Spaide, R. F., Curcio, C. A., Malek, G. & Imamura, Y. Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology 117, 303\u2013312 (2010).","journal-title":"Ophthalmology"},{"key":"97771_CR4","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.ophtha.2016.02.009","volume":"123","author":"U Greferath","year":"2016","unstructured":"Greferath, U., Guymer, R. H., Vessey, K. A., Brassington, K. & Fletcher, E. L. Correlation of histologic features with in vivo imaging of reticular pseudodrusen. Ophthalmology 123, 1320\u20131331 (2016).","journal-title":"Ophthalmology"},{"key":"97771_CR5","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1167\/iovs.62.1.33","volume":"62","author":"L Chen","year":"2021","unstructured":"Chen, L., Messinger, J. D., Kar, D., Duncan, J. L. & Curcio, C. A. Biometrics, impact, and significance of basal linear deposit and subretinal drusenoid deposit in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 62, 33 (2021).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"97771_CR6","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1097\/IAE.0000000000002657","volume":"40","author":"L Chen","year":"2020","unstructured":"Chen, L. et al. Subretinal drusenoid deposit in age related macular degeneration: Histologic insights into initiation, progression to atrophy, and imaging. Retina 40, 618\u2013631 (2020).","journal-title":"Retina"},{"key":"97771_CR7","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.survophthal.2018.05.005","volume":"63","author":"RF Spaide","year":"2018","unstructured":"Spaide, R. F., Ooto, S. & Curcio, C. A. Subretinal drusenoid deposits AKA pseudodrusen. Surv. Ophthalmol. 63, 782\u2013815 (2018).","journal-title":"Surv. Ophthalmol."},{"key":"97771_CR8","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1097\/IAE.0b013e31827e25e0","volume":"33","author":"CA Curcio","year":"2013","unstructured":"Curcio, C. A. et al. Subretinal drusenoid deposits in non-neovascular age-related macular degeneration: Morphology, prevalence, topography, and biogenesis model. Retina 33, 265\u2013276 (2013).","journal-title":"Retina"},{"key":"97771_CR9","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1007\/s00417-016-3375-1","volume":"254","author":"F Alten","year":"2016","unstructured":"Alten, F., Heiduschka, P., Clemens, C. R. & Eter, N. Exploring choriocapillaris under reticular pseudodrusen using OCT-Angiography. Graefes. Arch. Clin. Exp. Ophthalmol. 254, 2165\u20132173 (2016).","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"97771_CR10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ajo.2016.10.005","volume":"174","author":"PL Nesper","year":"2017","unstructured":"Nesper, P. L., Soetikno, B. T. & Fawzi, A. A. Choriocapillaris nonperfusion is associated with poor visual acuity in eyes with reticular pseudodrusen. Am. J. Ophthalmol. 174, 42\u201355 (2017).","journal-title":"Am. J. Ophthalmol."},{"key":"97771_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1167\/iovs.61.10.19","volume":"61","author":"M Sassmannshausen","year":"2020","unstructured":"Sassmannshausen, M. et al. Longitudinal analysis of structural and functional changes in presence of reticular pseudodrusen associated with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 61, 19 (2020).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"97771_CR12","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.oret.2019.10.012","volume":"4","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. et al. Lifecycles of individual subretinal drusenoid deposits and evolution of outer retinal atrophy in age-related macular degeneration. Ophthalmol. Retina. 4, 274\u2013283 (2020).","journal-title":"Ophthalmol. Retina."},{"key":"97771_CR13","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1097\/IAE.0b013e31829c3765","volume":"33","author":"RF Spaide","year":"2013","unstructured":"Spaide, R. F. Outer retinal atrophy after regression of subretinal drusenoid deposits as a newly recognized form of late age-related macular degeneration. Retina 33, 1800\u20131808 (2013).","journal-title":"Retina"},{"key":"97771_CR14","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1007\/s00417-018-4053-2","volume":"256","author":"JL Lauermann","year":"2018","unstructured":"Lauermann, J. L. et al. Prevalences of segmentation errors and motion artifacts in OCT-angiography differ among retinal diseases. Graefes. Arch. Clin. Exp. Ophthalmol. 256, 1807\u20131816 (2018).","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"97771_CR15","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S0161-6420(13)38012-9","volume":"98","author":"Early Treatment Diabetic Retinopathy Study Research Group","year":"1991","unstructured":"Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs\u2014An extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 98, 786\u2013806 (1991).","journal-title":"Ophthalmology"},{"key":"97771_CR16","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s12886-020-01467-0","volume":"20","author":"CA Curcio","year":"2020","unstructured":"Curcio, C. A. et al. Functionally validated imaging endpoints in the Alabama study on early age-related macular degeneration 2 (ALSTAR2): Design and methods. BMC Ophthalmol. 20, 96 (2020).","journal-title":"BMC Ophthalmol."},{"key":"97771_CR17","doi-asserted-by":"publisher","first-page":"5009","DOI":"10.1167\/iovs.11-7235","volume":"52","author":"S Schmitz-Valckenberg","year":"2011","unstructured":"Schmitz-Valckenberg, S. et al. Reticular drusen associated with geographic atrophy in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 52, 5009\u20135015 (2011).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"97771_CR18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ajo.2016.07.023","volume":"170","author":"RF Spaide","year":"2016","unstructured":"Spaide, R. F. Choriocapillaris flow features follow a power law distribution: Implications for characterization and mechanisms of disease progression. Am. J. Ophthalmol. 170, 58\u201367 (2016).","journal-title":"Am. J. Ophthalmol."},{"key":"97771_CR19","unstructured":"Phansalkar, N., More, S., Sabale, A., Joshi, M. Adaptive local thresholding for detection of nuclei in diversity stained cytology images. In 2011 International Conference on Communications and Signal Processing: IEEE, 218\u2013220 (2011)."},{"key":"97771_CR20","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.ajo.2020.02.003","volume":"213","author":"Z Chu","year":"2020","unstructured":"Chu, Z. et al. Quantification of choriocapillaris with Phansalkar\u2019s local thresholding: Pitfalls to avoid. Am. J. Ophthalmol. 213, 161\u2013176 (2020).","journal-title":"Am. J. Ophthalmol."},{"key":"97771_CR21","doi-asserted-by":"publisher","first-page":"658","DOI":"10.21037\/qims.2018.08.10","volume":"8","author":"Q Zhang","year":"2018","unstructured":"Zhang, Q. et al. Accurate estimation of choriocapillaris flow deficits beyond normal intercapillary spacing with swept source OCT angiography. Quant. Imaging Med. Surg. 8, 658\u2013666 (2018).","journal-title":"Quant. Imaging Med. Surg."},{"key":"97771_CR22","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1167\/iovs.05-0892","volume":"47","author":"S Schmitz-Valckenberg","year":"2006","unstructured":"Schmitz-Valckenberg, S. et al. Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD. Invest. Ophthalmol. Vis. Sci. 47, 2648\u20132654 (2006).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"97771_CR23","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1136\/bjophthalmol-2014-305339","volume":"99","author":"F Alten","year":"2015","unstructured":"Alten, F. & Eter, N. Current knowledge on reticular pseudodrusen in age-related macular degeneration. Br. J. Ophthalmol 99, 717\u2013722 (2015).","journal-title":"Br. J. Ophthalmol"},{"key":"97771_CR24","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.ophtha.2017.09.028","volume":"125","author":"SR Sadda","year":"2018","unstructured":"Sadda, S. R. et al. Consensus definition for atrophy associated with age-related macular degeneration on optical coherence tomography: CAM Report 3. Ophthalmology 125, 537\u2013548 (2018).","journal-title":"Ophthalmology"},{"key":"97771_CR25","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.ophtha.2019.09.035","volume":"127","author":"RH Guymer","year":"2020","unstructured":"Guymer, R. H. et al. Incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration: Classification of atrophy meeting report 4. Ophthalmology 127, 394\u2013409 (2020).","journal-title":"Ophthalmology"},{"key":"97771_CR26","volume-title":"Biostatistical Analysis","author":"J Zar","year":"1984","unstructured":"Zar, J. Biostatistical Analysis 2nd edn. (Prentice-Hall, 1984).","edition":"2"},{"key":"97771_CR27","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.ajo.2007.03.007","volume":"143","author":"S Peters","year":"2007","unstructured":"Peters, S. et al. Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab. Am. J. Ophthalmol 143, 995\u20131002 (2007).","journal-title":"Am. J. Ophthalmol"},{"key":"97771_CR28","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1167\/iovs.18-24522","volume":"60","author":"T Hikichi","year":"2019","unstructured":"Hikichi, T. & Agarie, M. Reduced vessel density of the choriocapillaris during anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 60, 1088\u20131095 (2019).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"97771_CR29","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.ophtha.2013.08.015","volume":"121","author":"JE Grunwald","year":"2014","unstructured":"Grunwald, J. E. et al. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology 121, 150\u2013161 (2014).","journal-title":"Ophthalmology"},{"key":"97771_CR30","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1007\/s00417-017-3813-8","volume":"255","author":"F Alten","year":"2017","unstructured":"Alten, F. et al. Signal reduction in choriocapillaris and segmentation errors in spectral domain OCT angiography caused by soft drusen. Graefes. Arch. Clin. Exp. Ophthalmol. 255, 2347\u20132355 (2017).","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"97771_CR31","first-page":"2857","volume":"35","author":"RS Ramrattan","year":"1994","unstructured":"Ramrattan, R. S. et al. Morphometric analysis of Bruch\u2019s membrane, the choriocapillaris, and the choroid in aging. Invest. Ophthalmol. Vis Sci. 35, 2857\u20132864 (1994).","journal-title":"Invest. Ophthalmol. Vis Sci."},{"key":"97771_CR32","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ajo.2018.12.025","volume":"200","author":"F Zheng","year":"2019","unstructured":"Zheng, F. et al. Age-dependent changes in the macular choriocapillaris of normal eyes imaged with swept-source optical coherence tomography angiography. Am. J. Ophthalmol. 200, 110\u2013122 (2019).","journal-title":"Am. J. Ophthalmol."},{"key":"97771_CR33","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1097\/IAE.0000000000002990","volume":"41","author":"F Corvi","year":"2021","unstructured":"Corvi, F. et al. Choriocapillaris flow deficit as a risk factor for progression of age-related macular degeneration. Retina 41, 686\u2013693 (2021).","journal-title":"Retina"},{"key":"97771_CR34","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.21037\/qims-20-340","volume":"10","author":"R Laiginhas","year":"2020","unstructured":"Laiginhas, R., Cabral, D. & Falc\u00e3o, M. Evaluation of the different thresholding strategies for quantifying choriocapillaris using optical coherence tomography angiography. Quant. Imaging Med. Surg. 10, 1994\u20132005 (2020).","journal-title":"Quant. Imaging Med. Surg."},{"key":"97771_CR35","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1167\/tvst.9.8.44","volume":"9","author":"PX Braun","year":"2020","unstructured":"Braun, P. X. et al. Using the pathophysiology of dry AMD to guide binarization of the choriocapillaris on OCTA: A model. Trans. Vis. Sci. Tech. 9, 44 (2020).","journal-title":"Trans. Vis. Sci. Tech."},{"key":"97771_CR36","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1097\/IAE.0000000000002866","volume":"40","author":"G Ledesma-Gil","year":"2020","unstructured":"Ledesma-Gil, G., Fernandez-Avellaneda, P. & Spaide, R. F. Swept-source optical coherence tomography angiography image compensation of the choriocapillaris induces artifacts. Retina 40, 1865\u20131872 (2020).","journal-title":"Retina"},{"key":"97771_CR37","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ajo.2019.08.026","volume":"208","author":"I Byon","year":"2019","unstructured":"Byon, I., Nassisi, M., Borrelli, E. & Sadda, S. R. Impact of slab selection on quantification of choriocapillaris flow deficits by optical coherence tomography angiography. Am. J. Ophthalmol. 208, 397\u2013405 (2019).","journal-title":"Am. J. Ophthalmol."},{"key":"97771_CR38","doi-asserted-by":"publisher","first-page":"751","DOI":"10.3390\/jcm10040751","volume":"10","author":"J Scharf","year":"2021","unstructured":"Scharf, J., Corradetti, G., Corvi, F., Sadda, S. & Sarraf, D. Optical coherence tomography angiography of the choriocapillaris in age-related macular degeneration. J. Clin. Med. 10, 751 (2021).","journal-title":"J. Clin. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97771-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97771-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97771-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T15:18:32Z","timestamp":1670080712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97771-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["97771"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-97771-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]},"assertion":[{"value":"13 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Christoph Clemens and Florian Alten are consultants to Bayer, Nicole Eter is a consultant to Heidelberg Engineering, Novartis, Bayer, Sanofi Aventis, Allergan, Bausch and Lomb. Jost Lauermann and Boris Schmitz: None.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18227"}}