{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:08Z","timestamp":1760060048309,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Eye Institute (NEI) of the National Institutes of Health","award":["R01EY024315","K12TR004522"],"award-info":[{"award-number":["R01EY024315","K12TR004522"]}]},{"name":"National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health","award":["R01EY024315","K12TR004522"],"award-info":[{"award-number":["R01EY024315","K12TR004522"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo.<\/jats:p>","DOI":"10.3390\/diagnostics15151904","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal High-Resolution Imaging of Retinal Sequelae of a Choroidal Nevus"],"prefix":"10.3390","volume":"15","author":[{"given":"Kaitlyn A.","family":"Sapoznik","sequence":"first","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"},{"name":"College of Optometry, University of Houston, Houston, TX 77204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5348-035X","authenticated-orcid":false,"given":"Stephen A.","family":"Burns","sequence":"additional","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd D.","family":"Peabody","sequence":"additional","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-8753","authenticated-orcid":false,"given":"Lucie","family":"Sawides","sequence":"additional","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"},{"name":"Instituto de \u00d3ptica, Consejo Superior de Investigaciones Cient\u00edficas, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany R.","family":"Walker","sequence":"additional","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Gast","sequence":"additional","affiliation":[{"name":"School of Optometry, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.ophtha.2005.06.011","article-title":"Estimating the risk of malignant transformation of a choroidal nevus","volume":"112","author":"Singh","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1016\/j.ophtha.2011.05.007","article-title":"Prevalence and characteristics of choroidal nevi: The multi-ethnic study of atherosclerosis","volume":"118","author":"Greenstein","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.ophtha.2007.12.022","article-title":"Choroidal Nevi in Adult Chinese","volume":"115","author":"Jonas","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1001\/archophthalmol.2008.625","article-title":"Prevalence and Characteristics of Choroidal Nevi in an Asian vs White Population","volume":"127","author":"Ng","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1001\/archophthalmol.2009.151","article-title":"Choroidal nevus transformation into melanoma: Analysis of 2514 consecutive cases","volume":"127","author":"Shields","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0008-4182(04)80005-X","article-title":"Clinical factors in the identification of small choroidal melanoma","volume":"39","author":"Shields","year":"2004","journal-title":"Can. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/BF00164669","article-title":"Indocyanine green angiography of choroidal tumors","volume":"233","author":"Sallet","year":"1995","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1097\/IAE.0000000000002440","article-title":"Choroidal nevus imaging features in 3806 cases and risk factors for transformation into melanoma in 2355 cases: The 2020 Taylor R. Smith and Victor T. Curtin Lecture","volume":"39","author":"Shields","year":"2019","journal-title":"Retina"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/ICU.0000000000000361","article-title":"Choroidal nevus: A review of prevalence, features, genetics, risks, and outcomes","volume":"28","author":"Chien","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jcjo.2023.07.005","article-title":"Advances in multimodal imaging for diagnosis of pigmented ocular fundus lesions","volume":"59","author":"Verbeek","year":"2024","journal-title":"Can. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1001\/jamaophthalmol.2024.6064","article-title":"Pixel Intensity to Estimate Choroidal Tumor Thickness Using 2-Dimensional Ultra-Widefield Images","volume":"143","author":"Yu","year":"2025","journal-title":"JAMA Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41433-022-02143-x","article-title":"Can the MOLES acronym and scoring system improve the management of patients with melanocytic choroidal tumours?","volume":"37","author":"Damato","year":"2023","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/eye.1990.51","article-title":"Tumour-associated retinal pigment epitheliopathy","volume":"4","author":"Damato","year":"1990","journal-title":"Eye"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Naylor, A., Hopkins, A., Hudson, N., and Campbell, M. (2019). Tight Junctions of the Outer Blood Retina Barrier. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010211"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0161-6420(82)34711-9","article-title":"Visual loss associated with choroidal nevi","volume":"89","author":"Gonder","year":"1982","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1001\/archopht.125.11.1501","article-title":"Visual Acuity in 3422 Consecutive Eyes With Choroidal Nevus","volume":"125","author":"Shields","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/ICB.0000000000000024","article-title":"Leaking choroidal nevus treated with focal laser photocoagulation","volume":"8","author":"Goldman","year":"2014","journal-title":"Retin. Cases Brief Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/ICB.0b013e3180653d53","article-title":"Focal laser photocoagulation for polypoidal choroidal vasculopathy associated with choroidal nevus","volume":"2","author":"Querques","year":"2008","journal-title":"Retin. Cases Brief Rep."},{"key":"ref_19","first-page":"25158414231160689","article-title":"Photoreceptor outer segment layer thinning as a biomarker in acute central serous chorioretinopathy","volume":"15","author":"Maltsev","year":"2023","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yoon, J., Han, J., Ko, J., Choi, S., Park, J.I., Hwang, J.S., Han, J.M., Jang, K., Sohn, J., and Park, K.H. (2022). Classifying central serous chorioretinopathy subtypes with a deep neural network using optical coherence tomography images: A cross-sectional study. Sci. Rep., 12.","DOI":"10.1038\/s41598-021-04424-z"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1167\/iovs.18-24244","article-title":"Polypoidal Choroidal Vasculopathy: Outer Retinal and Choroidal Changes and Neovascularization Development in the Fellow Eye","volume":"60","author":"Baek","year":"2019","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.preteyeres.2016.04.008","article-title":"Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes","volume":"53","author":"Khan","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.preteyeres.2018.08.002","article-title":"Adaptive optics imaging of the human retina","volume":"68","author":"Burns","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1001\/jamaophthalmol.2016.3633","article-title":"Photoreceptor Arrangement Changes Secondary to Choroidal Nevus","volume":"134","author":"Rodrigues","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3928\/23258160-20170329-12","article-title":"Adaptive Optics of Small Choroidal Melanoma","volume":"48","author":"Rodrigues","year":"2017","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1167\/iovs.16-20351","article-title":"High-Resolution Imaging of Intraretinal Structures in Active and Resolved Central Serous Chorioretinopathy","volume":"58","author":"Vogel","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3928\/23258160-20160229-10","article-title":"Multi-Modal Longitudinal Evaluation of Subthreshold Laser Lesions in Human Retina, Including Scanning Laser Ophthalmoscope-Adaptive Optics Imaging","volume":"47","author":"Wood","year":"2016","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/OPX.0000000000002004","article-title":"Case Report: Multimodal, Longitudinal Assessment of Retinal Structure and Function following Laser Retinal Injury","volume":"100","author":"Wang","year":"2023","journal-title":"Optom. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1364\/BOE.9.001323","article-title":"Enhanced retinal vasculature imaging with a rapidly configurable aperture","volume":"9","author":"Luo","year":"2018","journal-title":"Biomed. Opt. Express"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/tvst.12.11.16","article-title":"Retinal Arteriolar Wall Remodeling in Diabetes Captured With AOSLO","volume":"12","author":"Sapoznik","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Warner, R.L., de Castro, A., Sawides, L., Gast, T., Sapoznik, K., Luo, T., and Burns, S.A. (2020). Full-field flicker evoked changes in parafoveal retinal blood flow. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73032-0"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1167\/iovs.62.14.29","article-title":"Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels","volume":"62","author":"Warner","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"A265","DOI":"10.1364\/JOSAA.27.00A265","article-title":"Adaptive optics scanning laser ophthalmoscope with integrated wide-field retinal imaging and tracking","volume":"27","author":"Ferguson","year":"2010","journal-title":"J. Opt. Soc. Am. A Opt. Image Sci. Vis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1167\/iovs.17-21793","article-title":"Alterations to the Foveal Cone Mosaic of Diabetic Patients","volume":"58","author":"Sawides","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1167\/iovs.14-14542","article-title":"In vivo imaging of human cone photoreceptor inner segments","volume":"55","author":"Scoles","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6096017","DOI":"10.1155\/2021\/6096017","article-title":"Significance of Hyperreflective Foci as an Optical Coherence Tomography Biomarker in Retinal Diseases: Characterization and Clinical Implications","volume":"2021","author":"Fragiotta","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12974-024-03064-0","article-title":"Macrophages coordinate immune response to laser-induced injury via extracellular traps","volume":"21","author":"Conedera","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1167\/iovs.07-1322","article-title":"In Vivo Visualization of Dendritic Cells, Macrophages, and Microglial Cells Responding to Laser-Induced Damage in the Fundus of the Eye","volume":"49","author":"Eter","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100475","DOI":"10.1016\/j.xops.2024.100475","article-title":"Label-Free Imaging of Inflammation at the Level of Single Cells in the Living Human Eye","volume":"4","author":"Rui","year":"2024","journal-title":"Ophthalmol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1364\/JOSAA.24.001313","article-title":"Large-field-of-view, modular, stabilized, adaptive-optics-based scanning laser ophthalmoscope","volume":"24","author":"Burns","year":"2007","journal-title":"J. Opt. Soc. Am. A Opt. Image Sci. Vis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/OPX.0b013e318253e081","article-title":"A Clinical Planning Module for Adaptive Optics SLO Imaging","volume":"89","author":"Huang","year":"2012","journal-title":"Optom. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1167\/iovs.16-19503","article-title":"In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy","volume":"57","author":"Tam","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1167\/iovs.08-2618","article-title":"In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic","volume":"50","author":"Morgan","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1364\/BOE.4.001710","article-title":"In vivo dark-field imaging of the retinal pigment epithelium cell mosaic","volume":"4","author":"Scoles","year":"2013","journal-title":"Biomed. Opt. Express"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1167\/iovs.06-1450","article-title":"High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease","volume":"48","author":"Roorda","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"OCT533","DOI":"10.1167\/iovs.16-19106","article-title":"3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina","volume":"57","author":"Liu","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","first-page":"491","article-title":"Microglial cell activation following retinal detachment: A comparison between species","volume":"11","author":"Lewis","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1167\/iovs.12-11204","article-title":"Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser","volume":"54","author":"Chidlow","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.1167\/iovs.08-1928","article-title":"Healing of Retinal Photocoagulation Lesions","volume":"49","author":"Paulus","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"RP98662","DOI":"10.7554\/eLife.98662","article-title":"Photoreceptor loss does not recruit neutrophils despite strong microglial activation","volume":"13","author":"Power","year":"2025","journal-title":"eLife"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/nprot.2017.032","article-title":"Comprehensive analysis of mouse retinal mononuclear phagocytes","volume":"12","author":"Scholz","year":"2017","journal-title":"Nat. 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