Choroidal vascular changes in eyes with acute macular neuroretinopathy and paracentral acute middle maculopathy: new insights

Choroidal vascular changes in eyes with acute macular neuroretinopathy and paracentral acute middle maculopathy: new insights | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Choroidal vascular changes in eyes with acute macular neuroretinopathy and paracentral acute middle maculopathy: new insights Nicola Valsecchi, Matteo Elifani, Chiara Veronese, Emilia Maggio, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7225320/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Feb, 2026 Read the published version in BMC Ophthalmology → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose : To assess choroidal vasculature changes in acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) during the acute and resolution phases. Methods : Retrospective, cross-sectional “case-control” comparison study. Twenty eyes from 20 patients were analyzed: 5 with AMN and 15 with PAMM. Also, 30 healthy age-matched controls were included. We retrospectively analyzed clinical records and spectral-domain optical coherence tomography (SD-OCT) scans from patients affected by AMN and PAMM. Choroidal assessment was performed using an automated algorithm, binarized into stromal choroidal areas (SCA) and luminal choroidal areas (LCA). CVI was calculated as the ratio of LCA to total choroidal area (TCA). Sub-foveal choroidal thickness was measured too. Statistical analysis was done using non-parametric tests. Results : Patient’s median age was 52 years (IQR = 30-65.5), and 54% were female. AMN eyes showed significantly increased subfoveal choroidal thickness (SFCT), TCA, SCA, and LCA compared to PAMM and controls (p=0.041, p=0.005, p=0.006, p=0.010 respectively). No significant difference in CVI was observed between the groups (p=0.605). After disease resolution, SFCT, TCA, SCA, and LCA significantly decreased in AMN eyes (p=0.043, p=0.040, p=0.040, p=0.040 respectively), while no changes were observed in PAMM (p>0.05). Also, AMN eyes exhibited higher SFCT, TCA, SCA and LCA compared to controls and PAMM eyes (p<0.05) even after resolution. Conclusions : Increased choroidal thickness is a characteristic feature of AMN, with reduction observed after resolution. On the other hand, no changes in choroidal parameters were observed in PAMM, suggesting distinct pathophysiological mechanisms between the two conditions. Choroid AMN PAMM pathogenesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Acute macular neuroretinopathy (AMN) is a rare macular condition first described by Bos and Deutman in 1975, with a prevalence ranging from 0.66 to 8.97 cases per 100.000 visits 1 , 2 . Clinically, it is characterized by the acute onset of photopsia and paracentral scotoma, accompanied by reduction in visual acuity. It primarily affects young adults, with a higher prevalence among females and Caucasians. 3 Among the identified triggering factors, a history of viral symptoms or fever, and the use of oral contraceptives were the most frequently reported. 4 The advent of optical coherence tomography (OCT) has significantly improved the characterization of AMN. 5 In the acute phase, the condition is distinguished by hyperreflectivity of the outer plexiform layer, followed by thinning of the outer nuclear layer and disruption of the photoreceptor layer and retinal pigment epithelium (RPE). On the other hand, paracentral acute middle maculopathy (PAMM) is an OCT finding associated with vaso-occlusive retinal conditions of both arterial and venous origin. 6 Initially classified as a variant of AMN, OCT imaging enabled its differentiation based on distinct features, such as the hyperreflectivity of the inner nuclear layer (INL), which subsequently results in thinning of the INL. This distinction has led to the classification of PAMM as a separate clinical entity from AMN. 7 Although AMN and PAMM are distinct conditions, they share overlapping characteristics, especially with regard to their presumed ischemic etiology. Furthermore, PAMM and AMN can coexist within the same eye, suggesting a common pathophysiologic mechanism. 8 Numerous studies utilizing OCT angiography (OCTA) have provided strong evidence that the deep capillary plexus (DCP) is the primary site of damage in PAMM, with associated reductions in vascular flow. 9 , 10 Conversely, the precise localization of ischemic insult in AMN remains a subject of ongoing debate. Historically, capillary flow deficit at the level of the DCP was considered the primary pathogenic mechanism in AMN. 11 , 12 However, over the past years, increasing attention has shifted toward alterations in the choriocapillaris (CC). 13 , 14 Recently, Hashimoto et al. reported a single case of bilateral AMN in a 15-year-old male, characterized by an increase in subfoveal choroidal thickness (SFCT) and alterations in choroidal circulation during the acute phase of the disease. These findings resolved over time, supporting the hypothesis of an involvement of the choroidal vasculature. 15 Also, von der Burchard et al. identified a perfusion deficit in the CC and choroidal layer in AMN, suggesting that choroidal hypoperfusion, rather than the previously believed hypoperfusion of the deep capillary plexus (DCP), is the primary mechanism underlying AMN. However, the study lacked longitudinal assessment of patients before and after resolution of the acute event, and they did not include OCT parameters such as choroidal thickness or the choroidal vascularity index (CVI). Therefore, the present study aimed to assess the changes in the choroidal vasculature in AMN by quantifying the choroidal thickness and the CVI in the acute phase and after resolution of the disease. To improve measurement accuracy, we used a previously validated artificial intelligence (AI)-based software. 16 In addition, we sought to compare these findings with a cohort of PAMM cases to further refine the distinction between these two clinical entities. Material and methods Study Population This retrospective, observational, multicentric study included patients diagnosed with PAMM and AMN lesions, based on clinical examination and OCT findings. Patients were recruited from the Unit of Ophthalmology, IRCCS University of Bologna (Bologna, Italy) and from the Department of Ophthalmology, IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy). Institutional review board approval was obtained from the respective referral centers for the retrospective chart review. The study adhered to the principles of the Declaration of Helsinki, and all participants provided written informed consent. Diagnostic criteria for acute AMN included the presence of an acute paracentral scotoma corresponding to hyperreflective lesions in the outer retina, accompanied by disruption of the ellipsoid zone (EZ). For PAMM, diagnostic criteria involved a recent history of acute paracentral scotomas, with or without deep intraretinal whitening on fundus examination, hyporeflective wedge-shaped lesions on near infrared reflectance (NIR) imaging, and corresponding hyperreflective lesions in the INL on OCT, as previously described. 8 Resolution of the acute phase was considered at least 3 months after the event, with the disappearance of acute signs on OCT scans. Exclusion criteria were significant media opacities, other macular conditions (e.g., intermediate or late-stage age-related macular degeneration or diabetic macular edema), poor-quality imaging, any prior ocular surgeries (except cataract surgery), and high myopia. A cohort of healthy age-matched controls was also included, following the same exclusion criteria. Ophthalmological Assessment At baseline and follow-up visits after disease resolution, a comprehensive ophthalmological examination was performed, which included measurement of BCVA, slit-lamp biomicroscopy, intraocular pressure (IOP) assessment, dilated fundus examination using a 90D indirect lens, and spectral-domain (SD)-OCT imaging (Spectralis HRA-OCT; Heidelberg Engineering GmbH, Heidelberg, Germany). BCVA was assessed using a Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. OCT Image Acquisition All subjects underwent the same SD-OCT protocol using the Heidelberg Spectralis (Heidelberg Engineering, Germany), which included a dense 20° x 15° raster scan with 145 B-scans spaced 30 µm apart, along with two vertical and horizontal single scans centered on the fovea (with automatic real-time values of at least 14 or higher). OCTA using Carl Zeiss Meditec (Optovue Inc., Fremont, California, USA) or Heidelberg Spectralis was performed when available. Registered and tracked OCT scans from the first and last available visits were obtained for each patient. The subfoveal choroidal thickness (SFCT) was manually measured as the vertical distance between the hyperreflective line of the Bruch membrane and the inner scleral surface using the caliper tool in the image analysis software. Measurements were performed by two independent observers (E.M, M.E.), with discrepancies resolved by a third observer (M.M.). Choroidal Vascularity Index analysis To assess the CVI, SD-OCT (Heidelberg Engineering, Heidelberg, Germany) images were used. OCT scans were performed between 9:00 AM and 12:00 PM to minimize diurnal variation effects on choroidal parameters. Registered and tracked OCT scans were used to assess the choroidal vasculature at baseline and after resolution. CVI was measured using an AI-based automated algorithm that included shadow compensation, denoising, localization of the inner and outer choroidal boundaries, and segmentation of the choroidal region from the rest of the scan. 16 Binarization of the choroid generated bright regions labeled as stromal choroidal areas (SCA) and dark regions labeled as luminal choroidal areas (LCA). CVI was calculated as the ratio of the luminal choroidal area to the total choroidal area (TCA). See Fig. 1 . Statistical Analysis Given the small sample sizes and the non-normal distribution of the data, non-parametric tests were employed. As variables were not normally distributed, they were reported as medians with interquartile ranges (IQR). Fisher’s exact test was used to assess associations between categorical variables. The Kruskal-Wallis test was applied to compare choroidal biomarkers among the three groups, and pairwise comparisons using the Dunn-Bonferroni approach were performed for significant variables. The Wilcoxon signed-rank test was used to compare choroidal biomarkers at baseline and after disease resolution. Mann-Whitney U tests were performed to compare AMN with healthy controls, PAMM with healthy controls, and PAMM with AMN eyes. P-values < 0.05 were considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics version 26. Results Demographic data A total of 20 eyes of 20 patients were included in the analysis, 5 eyes with AMN, and 15 eyes with PAMM. Also, 30 eyes of 30 healthy age-matched controls were included in the analysis. Demographics are shown in Table 1 . Table 1 Demographic data and choroidal biomarkers in acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAMM), and healthy age-matched controls. Controls (n = 30) PAMM (n = 15) AMN (n = 5) P value Age, median ± IQR 51 (28–65.5) 56 (48–68) 46 (29 -48.5) 0.078 Sex female, number (%) 14 (46.67%) 9 (60%) 4 (80%) 0.328 SFCT, 𝜇m median (IQR) 280.5 (231-352.25) 277 (217.75–334) 520 (348.5–573.5) 0.041 TCA, mm2 median (IQR) 1.55 (1.28–1.94) 1.67 (1.22–1.80) 2.69 (2.23–3.78) 0.006 SCA, mm2 median (IQR) 0.58 (0.48–0.73) 0.66 (0.46–0.69) 1.01 (0.92–1.33) 0.005 LCA, mm2 median (IQR) 0.99 (0.76–1.16) 0.97 (0.76–1.10) 1.67 (1.30–2.44) 0.010 CVI, % median (IQR) 62 (59.75-65) 62 (58–63) 62 (58.5–65) 0.605 SFCT = subfoveal choroidal thickness, TCA = total choroidal area, SCA = stromal choroidal area, LCA = luminal choroidal area, CVI = choroidal vascularity index, IQR = interquartile range. No differences in terms of age and sex were observed between the three groups. Median visual acuity was 0.1 LogMar (IQR = 0.05–0.2) in the AMN group and 0.6 LogMar (IQR = 0.2–0.8) in the PAMM group. In the AMN group, one patient underwent a previous bone marrow transplant for acute myeloid leukemia, and one patient had a previous flu-like illness. The remaining three patients did not present concomitant comorbidities at the time of the acute event. In the PAMM group, 5 patients had a concomitant branch retinal artery occlusion (BRAO), 2 patients had concomitant central retinal artery occlusion (CRAO), 3 patients had central retinal vein occlusion (CRVO), and 1 patient branch retinal vein occlusion (BRVO). The remaining 4 patients presented isolated PAMM. Among these patients, two did not have any concomitant comorbidities, one patient had a history of ischemic stroke, and one patient had a homolateral carotid artery stenosis. Choroidal parameters in AMN, PAMM, and healthy age-matched controls Eyes with AMN presented an increased SFCT, TCA, SCA, and LCA compared to PAMM and controls. After Dunn-Bonferroni correction, TCA, SCA, and LCA remained statistically significant when comparing AMN and PAMM (p = 0.010, p = 0.004, p = 0.011 respectively), and when comparing AMN and age-matched controls (p = 0.006, p = 0.016, p = 0.012 respectively). On the other hand, SFCT was significantly increased in AMN eyes compared to PAMM (p = 0.046), and it was close to significance when comparing AMN to healthy age-matched controls (p = 0.056). No significant differences in CVI were observed among the three groups. See Table 1 and Fig. 2 . Choroidal parameters after resolution After a median follow-up of 35.52 weeks (range 12–46 weeks), BCVA improved to 0 (IQR = 0-0.05) LogMar in the AMN group and to 0.3 (IQR = 0.1–0.6) LogMar in the PAMM group. SFCT, TCA, SCA, and LCA significantly decreased in AMN eyes. Choroidal thickness reduction after resolution of the acute event was observed in 100% of our cases in the AMN group. CVI presented a slight decrease that did not reach statistical significance. Also, PAMM eyes presented a reduction in SFCT, TCA, SCA, LCA, and CVI, even though the results were not statistically significant. S ee Table 2 . Table 2 Comparison of choroidal parameters after resolution in acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAMM), and healthy age-matched controls. Group Baseline Resolution P value Acute macular neuroretinopathy (AMN) SFCT, 𝜇m median (IQR) 520 (348.5–573.5) 432 (254.5-481.5) 0.043 TCA, mm2 median (IQR) 2.69 (2.23–3.78) 1.91 (1.75–2.48) 0.040 SCA, mm2 median (IQR) 1.01 (0.92–1.33) 0.81 (0.65–0.98) 0.040 LCA, mm2 median (IQR) 1.67 (1.30–2.44) 1.19 (1.04–1.50) 0.040 CVI, % median (IQR) 62 (58.5–65) 60 (58-63.5) 0.465 Paracentral acute middle maculopathy (PAMM) SFCT, 𝜇m median (IQR) 277 (217.75–334) 260 (212.5–345) 0.064 TCA, mm2 median (IQR) 1.67 (1.22–1.80) 1.49 (1.16–2.05) 0.629 SCA, mm2 median (IQR) 0.66 (0.46–0.69) 0.55 (0.45–0.82) 0.394 LCA, mm2 median (IQR) 0.97 (0.76–1.10) 0.83 (0.71-1-27 0.551 CVI, % median (IQR) 62 (58–63) 61 (0.59–0.63) 0.724 IQR = interquartile range, SFCT = subfoveal choroidal thickness, TCA = total choroidal area, SCA = stromal choroidal area, LCA = luminal choroidal area, CVI = choroidal vascularity index. Representative cases are shown in Fig. 3 and Fig. 4 . When comparing eyes with resolved AMN to healthy age-matched controls, we observed an increase in SFCT, TCA, SCA, and LCA, whereas no changes were observed for CVI. Also, AMN eyes showed a significant increase in SFCT, TCA, SCA and LCA compared to PAMM eyes. Conversely, PAMM eyes presented lower values of SFCT, TCA, SCA, LCA, and CVI compared to healthy controls, but the results were not statistically significant. See Table 3 . Table 3 Comparison of choroidal parameters in resolved acute macular neuroretinopathy (AMN), resolved paracentral acute middle maculopathy (PAMM), and healthy controls. Controls (n = 30) Resolved AMN (n = 5) P value SFCT, 𝜇m median (IQR) 280.5 (231-352.25) 432 (254.5-481.5) 0.028 TCA, mm2 median (IQR) 1.55 (1.28–1.94) 1.91 (1.75–2.48) 0.033 SCA, mm2 median (IQR) 0.58 (0.48–0.73) 0.81 (0.65–0.98) 0.025 LCA, mm2 median (IQR) 0.99 (0.76–1.16) 1.19 (1.04–1.50) 0.048 CVI, % median (IQR) 62 (59.75-65) 60 (58-63.5) 0.395 Controls (n = 30) Resolved PAMM (n = 15) P value SFCT, 𝜇m median (IQR) 280.5 (231-352.25) 260 (212.5–345) 0.500 TCA, mm2 median (IQR) 1.55 (1.28–1.94) 1.49 (1.16–2.05) 0.630 SCA, mm2 median (IQR) 0.58 (0.48–0.73) 0.55 (0.45–0.82) 0.885 LCA, mm2 median (IQR) 0.99 (0.76–1.16) 0.83 (0.71-1-27 0.647 CVI, % median (IQR) 62 (59.75-65) 61 (0.59–0.63) 0.537 Resolved AMN (n = 5) Resolved PAMM (n = 15) P value SFCT, 𝜇m median (IQR) 432 (254.5-481.5) 260 (212.5–345) 0.045 TCA, mm2 median (IQR) 1.91 (1.75–2.48) 1.49 (1.16–2.05) 0.034 SCA, mm2 median (IQR) 0.81 (0.65–0.98) 0.55 (0.45–0.82) 0.034 LCA, mm2 median (IQR) 1.19 (1.04–1.50) 0.83 (0.71-1-27 0.034 CVI, % median (IQR) 60 (58-63.5) 61 (0.59–0.63) 0.347 SFCT = subfoveal choroidal thickness, TCA = total choroidal area, SCA = stromal choroidal area, LCA = luminal choroidal area, CVI = choroidal vascularity index, IQR = interquartile range. Discussion In the present study, eyes with AMN presented an increased choroidal thickness compared to healthy eyes and PAMM. Also, AMN eyes showed a significant reduction of the choroidal thickness after resolution. On the other hand, we did not observe any significant differences in choroidal parameters in PAMM eyes before and after resolution. Furthermore, choroidal thickness was consistently increased in AMN eyes compared to healthy and PAMM eyes even after resolution. Several studies suggested that PAMM is the result of INL infarction due to vascular impairment occurring at the DCP. 17 In contrast, controversy still exists regarding the pathogenesis of AMN. Pecen et al. and Nemiroff et al. demonstrated capillary flow impairment at the level of the DCP in AMN. 18 , 19 Dansingani and Freund suggested that the perfusion deficit in AMN at the level of the DCP may not be severe enough to cause the typical alterations seen in PAMM. Instead, the characteristic changes at the photoreceptor level are likely a consequence of an ischemic event at the level of the CC. 20 Thanos and associates supported the theory that AMN may result from a vascular insult in the CC. 21 Furthermore, Lee et al. presented a case series of seven AMN patients, where OCTA imaging revealed flow deficits at the CC level during the acute phase of the disease. These perfusion abnormalities were correlated with the characteristic lesions observed on infrared imaging and, at the histological level, with the honeycomb-like microstructure of the choriocapillaris. 22 Recently, Duan et al. observed a topographic correlation between the neuroretinal lesions characteristic of AMN and the watershed zones at the choroidal level or areas of delayed choroidal perfusion, suggesting that increased vulnerability to hypoperfusion events may result from the presence of a double watershed zone, one between the DCP and the CC and the other at the choroidal watershed zones themselves. 23 Again, Hashimoto et al. described the case of a patient in which the choroid at the macula thickened at the onset of AMN and became thin with the regression of disease, suggesting that eyes with AMN may have blood flow impairments at the level of not only the CC but also the choroidal deeper layers. 15 Consistent with these studies, our findings indicate that choroidal thickness increases in AMN and decreases following the resolution of the acute event, whereas eyes with PAMM did not show significant changes in the choroidal vasculature. These results support the hypothesis that choroidal involvement occurs in AMN but not in PAMM, suggesting distinct pathophysiological mechanisms between the two conditions. As previously described, ocular pathologies characterized by an inflammatory process at the choroidal level show choroidal thickening during the acute phases, which then, in the remission phase, results in a reduction of the choroidal thickness. 24 Mrejen et al. reported an increase in choroidal thickness in acute posterior multifocal placoid pigment epitheliopathy (APMPPE), which subsequently decreased following resolution of the disease, suggesting that a transient ischemic choroiditis may contribute to secondary damage of the RPE. 25 Pellegrini et al. observed an increase in choroidal thickness, TCA, and CVI in eyes with multiple evanescent white dots syndrome (MEWDS), with these choroidal alterations being transient, suggesting that the observed increase in the vascular component is likely due to vascular stasis associated with the inflammatory process. 26 In our study, we observed an increase in SFCT, TCA, SCA, and LCA in AMN, supporting the hypothesis that an active inflammatory process might occur in the choroid during the acute phase. However, the CVI value remained unchanged, which may be due to a concurrent increase in both the vascular component, resulting from vascular stasis, and the stromal component, leading to no significant alteration in the CVI. It is noteworthy that in resolved cases of AMN, choroidal biomarkers remained significantly elevated compared to the control group. To the best of our knowledge, this is the first study to report such a finding. These results support the hypothesis of lasting alterations in both the choroidal vascular and stromal components following the acute inflammatory process in AMN. The main limitation of this study is the small patient cohort. Therefore, a larger sample size is needed to more effectively compare choroidal changes between AMN, PAMM, and healthy controls. Additionally, the relatively short follow-up period may not capture long-term changes; thus, extended follow-up is necessary to assess the lasting effects on choroidal vasculature in AMN and PAMM. Another limitation is the absence of OCTA images for all study participants, which prevented the analysis of the choriocapillaris (CC). Future research should incorporate multimodal imaging to correlate the CVI with OCTA parameters for a more comprehensive analysis. Conclusions Our study demonstrated an increase in choroidal thickness in AMN, which subsequently decreased following resolution. Also, eyes with AMN presented an increased choroidal thickness compared to healthy controls even after resolution, suggesting that choroidal alterations persist after recovery. On the other hand, no significant changes in choroidal parameters were observed in eyes with PAMM. These findings lend support to the hypothesis that AMN may primarily result from choroidal alterations, suggesting distinct pathophysiological mechanisms compared to PAMM. Further investigations are warranted to determine whether ischemic processes alone are responsible for the condition or if inflammatory mechanisms contribute to its development. Declarations Ethics approval and consent to participate: The study adhered to the principles of the Declaration of Helsinki, and all participants provided written informed consent and agreed to participate in the study. This study was approved by the Ethics Committee of Bologna, Italy (Cod CE: 53/2025/Oss/AOUBo). Consent for publication: All participants have given written permission to publish personal data. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding/Support: None. Contributorship Statement: Valsecchi N., Elifani M., Mete M., Maggio E., and Veronese C.conceived and designed the study. Valsecchi N., Elifani M., Maggio E., and Vupparaboina K. K. . acquired, analyzed, and interpreted the data . Valsecchi N.performed statistical analysis.Valsecchi N. and Elifani M. drafted the article.Mete M., Veronese C., Maggio E., Moramarco A., Fontana L., Chhablani J., and Pertile G. . revised it for intellectual content . The final version of the manuscript was approved by all the authors. Other Acknowledgments: None References Bos PJM, Deutman AF. Acute Macular Neuroretinopathy. Am J Ophthalmol . 1975;80(4):573-584. doi:10.1016/0002-9394(75)90387-6 Azar G, Bonnin S, Vasseur V, et al. Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy? J Clin Med . 2021;10(21):5038. doi:10.3390/jcm10215038 Miller MH, Spalton DJ, Fitzke FW, Bird AC. Acute macular neuroretinopathy. Ophthalmology . 1989;96(2):265-269. doi:10.1016/s0161-6420(89)32906-x Bhavsar KV, Lin S, Rahimy E, et al. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol . 2016;61(5):538-565. doi:10.1016/j.survophthal.2016.03.003 Fawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. Retina Phila Pa . 2012;32(8):1500-1513. doi:10.1097/IAE.0b013e318263d0c3 Moura-Coelho N, Gaspar T, Ferreira JT, Dutra-Medeiros M, Cunha JP. Paracentral acute middle maculopathy-review of the literature. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol . 2020;258(12):2583-2596. doi:10.1007/s00417-020-04826-1 Sarraf D, Rahimy E, Fawzi AA, et al. Paracentral Acute Middle Maculopathy: A New Variant of Acute Macular Neuroretinopathy Associated With Retinal Capillary Ischemia. JAMA Ophthalmol . 2013;131(10):1275. doi:10.1001/jamaophthalmol.2013.4056 Iovino C, Au A, Ramtohul P, et al. Coincident PAMM and AMN and Insights Into a Common Pathophysiology. Am J Ophthalmol . 2022;236:136-146. doi:10.1016/j.ajo.2021.07.004 Shah A, Rishi P, Chendilnathan C, Kumari S. OCT angiography features of paracentral acute middle maculopathy. Indian J Ophthalmol . 2019;67(3):417-419. doi:10.4103/ijo.IJO_1249_18 Casalino G, Williams M, McAvoy C, Bandello F, Chakravarthy U. Optical coherence tomography angiography in paracentral acute middle maculopathy secondary to central retinal vein occlusion. Eye . 2016;30(6):888-893. doi:10.1038/eye.2016.57 Rahimy E, Sarraf D. Paracentral acute middle maculopathy spectral-domain optical coherence tomography feature of deep capillary ischemia. Curr Opin Ophthalmol . 2014;25(3):207-212. doi:10.1097/ICU.0000000000000045 Rahimy E, Kuehlewein L, Sadda SR, Sarraf D. Paracentral Acute Middle Maculopathy: What We Knew Then and What We Know Now. Retina Phila Pa . 2015;35(10):1921-1930. doi:10.1097/IAE.0000000000000785 Thanos A, Faia LJ, Yonekawa Y, Randhawa S. Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy. JAMA Ophthalmol . 2016;134(11):1310-1314. doi:10.1001/jamaophthalmol.2016.3513 Lee SY, Cheng JL, Gehrs KM, et al. Choroidal Features of Acute Macular Neuroretinopathy via Optical Coherence Tomography Angiography and Correlation With Serial Multimodal Imaging. JAMA Ophthalmol . 2017;135(11):1177-1183. doi:10.1001/jamaophthalmol.2017.3790 Hashimoto Y, Saito W, Saito M, Hasegawa Y, Ishida S. Increased thickness and decreased blood flow velocity of the choroid in a patient with acute macular neuroretinopathy. BMC Ophthalmol . 2019;19(1):109. doi:10.1186/s12886-019-1123-0 Agrawal R, Wei X, Goud A, Vupparaboina KK, Jana S, Chhablani J. Influence of scanning area on choroidal vascularity index measurement using optical coherence tomography. Acta Ophthalmol (Copenh) . 2017;95(8):e770-e775. doi:10.1111/aos.13442 Fumi D, Ruggeri F, Fasciolo D, Antonello E, Burtini G, Abdolrahimzadeh S. Paracentral Acute Middle Maculopathy (PAMM) in Ocular Vascular Diseases—What We Know and Future Perspectives. Vision . 2025;9(1):19. doi:10.3390/vision9010019 Pecen PE, Smith AG, Ehlers JP. Optical Coherence Tomography Angiography of Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy. JAMA Ophthalmol . 2015;133(12):1478. doi:10.1001/jamaophthalmol.2015.4100 Nemiroff J, Sarraf D, Davila JP, Rodger D. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF ACUTE MACULAR NEURORETINOPATHY REVEALS DEEP CAPILLARY ISCHEMIA. Retin Cases Brief Rep . 2018;12(1):S12-S15. doi:10.1097/ICB.0000000000000706 Dansingani KK, Freund KB. Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy: Related and Distinct Entities. Am J Ophthalmol . 2015;160(1):1-3.e2. doi:10.1016/j.ajo.2015.05.001 Thanos A, Faia LJ, Yonekawa Y, Randhawa S. Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy. JAMA Ophthalmol . 2016;134(11):1310. doi:10.1001/jamaophthalmol.2016.3513 Lee SY, Cheng JL, Gehrs KM, et al. Choroidal Features of Acute Macular Neuroretinopathy via Optical Coherence Tomography Angiography and Correlation With Serial Multimodal Imaging. JAMA Ophthalmol . 2017;135(11):1177. doi:10.1001/jamaophthalmol.2017.3790 Duan J, An J, Li M, et al. Topographical Relationship Between Acute Macular Neuroretinopathy and Choroidal Watershed Zone or Patchy Choroidal Filling. Front Med . 2022;9:762609. doi:10.3389/fmed.2022.762609 Steiner M, Esteban-Ortega M del M, Muñoz-Fernández S. Choroidal and retinal thickness in systemic autoimmune and inflammatory diseases: A review. Surv Ophthalmol . 2019;64(6):757-769. doi:10.1016/j.survophthal.2019.04.007 Mrejen S, Sarraf D, Chexal S, Wald K, Freund KB. Choroidal Involvement in Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Ophthalmic Surg Lasers Imaging Retina . 2016;47(1):20-26. doi:10.3928/23258160-20151214-03 Pellegrini M, Veronese C, Bernabei F, et al. Choroidal Vascular Changes in Multiple Evanescent White Dot Syndrome. Ocul Immunol Inflamm . 2021;29(2):340-345. doi:10.1080/09273948.2019.1678650 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 11 Feb, 2026 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 21 Jan, 2026 Reviews received at journal 20 Jan, 2026 Reviews received at journal 19 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers agreed at journal 10 Aug, 2025 Reviewers invited by journal 09 Aug, 2025 Editor assigned by journal 09 Aug, 2025 Editor invited by journal 04 Aug, 2025 Submission checks completed at journal 01 Aug, 2025 First submitted to journal 01 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7225320","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":498930556,"identity":"6f89dfc8-79e8-4e13-8e3c-d7946168f320","order_by":0,"name":"Nicola Valsecchi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABK0lEQVRIie2RT2uDMBiHXxGSy1t6jbS4r6AE9gcKfhW9u9FT6UGGILiLbNeO7cM4AnoZ23WDHZTBvPQgDEphMBaFMawtXnfIAy95k/Ak+REAheI/ossqmoa20xTHNJQjYe1UyMJ9ivvbNIqRpFrYUXrOjgLWi9sofwfuXnNC9bJwA/BuIloW2+BtCq9V9Y6LUxPY+YOYL2HqdJWziHDLzcBbCeR2kn2gdufbET4xDuzCFavH3sMsgYS5BDjIZqKFAvWJr0WjmHkh8y0xig8o38CPBK2+GoUYeTmseDGYloBjvVGQgT2gyCzeNTNtmcVIMoEMffv2XmYhuLZkFoaYdpVnURb1ZoZmflXW20A4Tp4X9XpxaY6pzz/ny5nT/m0PtmeNHN5SKBQKxQA/w55oAFSablYAAAAASUVORK5CYII=","orcid":"","institution":"Alma Mater Studiorum University of Bologna","correspondingAuthor":true,"prefix":"","firstName":"Nicola","middleName":"","lastName":"Valsecchi","suffix":""},{"id":498930557,"identity":"c1889f48-9986-45e2-a5fb-70b7bd19eb26","order_by":1,"name":"Matteo Elifani","email":"","orcid":"","institution":"Alma Mater Studiorum University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Elifani","suffix":""},{"id":498930558,"identity":"54e4ea3d-505f-46f1-a08a-6b69452be9e7","order_by":2,"name":"Chiara Veronese","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna","correspondingAuthor":false,"prefix":"","firstName":"Chiara","middleName":"","lastName":"Veronese","suffix":""},{"id":498930559,"identity":"afa0098c-0bfa-4abb-9ff7-9701df848e2b","order_by":3,"name":"Emilia Maggio","email":"","orcid":"","institution":"IRCCS Sacro Cuore-Don Calabria Hospital","correspondingAuthor":false,"prefix":"","firstName":"Emilia","middleName":"","lastName":"Maggio","suffix":""},{"id":498930560,"identity":"301214b2-ab6a-4c26-a5ef-83cacc6d5345","order_by":4,"name":"Antonio Moramarco","email":"","orcid":"","institution":"Alma Mater Studiorum University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Moramarco","suffix":""},{"id":498930561,"identity":"04026186-9aff-4ed2-8f99-d0255d28e72a","order_by":5,"name":"Mohammed Abdul Rasheed","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"Abdul","lastName":"Rasheed","suffix":""},{"id":498930562,"identity":"b1fecd21-5b74-4f24-aca9-4d61d33d66ed","order_by":6,"name":"Grazie Pertile","email":"","orcid":"","institution":"IRCCS Sacro Cuore-Don Calabria Hospital","correspondingAuthor":false,"prefix":"","firstName":"Grazie","middleName":"","lastName":"Pertile","suffix":""},{"id":498930563,"identity":"1f400a9f-ef5e-489f-ad90-b9957e1d78b0","order_by":7,"name":"Kiran Kumar Vupparaboina","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Kiran","middleName":"Kumar","lastName":"Vupparaboina","suffix":""},{"id":498930564,"identity":"195a1741-618d-409a-9bfc-593081a12a4f","order_by":8,"name":"Jay Chhablani","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Jay","middleName":"","lastName":"Chhablani","suffix":""},{"id":498930565,"identity":"f33f45ab-b4a2-431d-8ae7-f310187e2b58","order_by":9,"name":"Luigi Fontana","email":"","orcid":"","institution":"Alma Mater Studiorum University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Luigi","middleName":"","lastName":"Fontana","suffix":""},{"id":498930566,"identity":"cb1157df-dc31-4328-b520-206e8d15eb39","order_by":10,"name":"Maurizio Mete","email":"","orcid":"","institution":"Alma Mater Studiorum University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Maurizio","middleName":"","lastName":"Mete","suffix":""}],"badges":[],"createdAt":"2025-07-27 09:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7225320/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7225320/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-026-04671-6","type":"published","date":"2026-02-11T15:57:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89232361,"identity":"80b47453-ffbd-4415-b84b-41de56d9e34d","added_by":"auto","created_at":"2025-08-17 14:24:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":318409,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChoroidal vascularity index analysis.\u003c/strong\u003eA) OCT foveal scan is shown; B) Choroidal area segmentation; C) Choroidal area binarization.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7225320/v1/3142cf84f4cc42ba9e6e43ed.png"},{"id":89233282,"identity":"97a3267a-b466-4185-b8e5-12c572bd948c","added_by":"auto","created_at":"2025-08-17 14:32:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":465242,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChoroidal vascularity index analysis in acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAMM), and healthy controls. \u003c/strong\u003eNote the increased choroidal thickness in a 34 years old female with AMN compared to a 32 years old female with PAMM, and a 30 years old healthy female.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7225320/v1/fe5d0e6d1f8e9c1c0f725756.png"},{"id":89232365,"identity":"c976992b-49c0-458d-94bf-ff6746770514","added_by":"auto","created_at":"2025-08-17 14:24:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":711875,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative case of acute macular neuroretinopathy (AMN) at presentation and after resolution. A) \u003c/strong\u003eNear-infrared (NIR) image at the presentation of the right eye in a 32 years old female: a wedge-shaped macular lesion (white arrow) with its apex directed toward the fovea is shown. \u003cstrong\u003eB) \u003c/strong\u003eSpectral-domain optical coherence tomography (SD-OCT) horizontal foveal scan shows a hyper-reflective band at the level of the outer plexiform layer (OPL) (white arrow). The subfoveal choroidal thickness (SFCT) is 520 𝜇m. \u003cstrong\u003eC) \u003c/strong\u003eAfter 10 months from the acute event, a 3mm x 3 mm macular cube optical coherence tomography angiography (OCTA) does not show alterations at the level of deep capillary plexus (DCP). \u003cstrong\u003eD) \u003c/strong\u003eOn the other hand, attenuation of the choriocapillaris (white box) is observed, which corresponds to the enface OCT scan \u003cstrong\u003eE) \u003c/strong\u003eat the level of the IS/OS-ellipsoid layer, revealing a wedge-shaped lesion (white box). \u003cstrong\u003eF)\u003c/strong\u003e SD-OCT horizontal foveal scan shows disruption of the ellipsoid zone and the interdigitation zone (white arrow). SFCT is 319 𝜇m.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7225320/v1/333b7c8fe0482864255fc42b.png"},{"id":89233288,"identity":"160792c9-527c-4a38-9806-9661043bd777","added_by":"auto","created_at":"2025-08-17 14:32:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":535783,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative case of paracentral acute middle maculopathy (PAMM) at presentation and after resolution): \u003c/strong\u003eMulticolor \u003cstrong\u003e(A) \u003c/strong\u003eand fundus autofluorescence \u003cstrong\u003e(B) \u003c/strong\u003edisplay the PAMM lesion in a 34 years old female. \u003cstrong\u003e(A) \u003c/strong\u003eShows a whitish lesion, and \u003cstrong\u003eB) \u003c/strong\u003eshows a hypoautofluorescent lesion. \u003cstrong\u003eC)\u003c/strong\u003eNear-infrared (NIR) and spectral-domain optical coherence tomography (SD-OCT) vertical foveal scan at presentation are shown\u003cstrong\u003e. \u003c/strong\u003eA placoid, hyperreflective band involving the inner nuclear layer with associated shadowing of outer layers is displayed. Subfoveal choroidal thickness (SFCT) is 334 𝜇m\u003cstrong\u003e(D)\u003c/strong\u003e. After 7 months from the acute event, thinning of the inner retinal layer is observed in the area of PAMM. SFCT is 316 𝜇m.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7225320/v1/531e58ea84cbdbc760f03db6.png"},{"id":102786468,"identity":"8805d39f-dc6a-4a75-93b1-e8108a879f6f","added_by":"auto","created_at":"2026-02-16 16:13:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2967365,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7225320/v1/7eac114d-e9e5-49fc-9366-09e19993fe07.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Choroidal vascular changes in eyes with acute macular neuroretinopathy and paracentral acute middle maculopathy: new insights","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute macular neuroretinopathy (AMN) is a rare macular condition first described by Bos and Deutman in 1975, with a prevalence ranging from 0.66 to 8.97 cases per 100.000 visits \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Clinically, it is characterized by the acute onset of photopsia and paracentral scotoma, accompanied by reduction in visual acuity. It primarily affects young adults, with a higher prevalence among females and Caucasians. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Among the identified triggering factors, a history of viral symptoms or fever, and the use of oral contraceptives were the most frequently reported. \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The advent of optical coherence tomography (OCT) has significantly improved the characterization of AMN.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e In the acute phase, the condition is distinguished by hyperreflectivity of the outer plexiform layer, followed by thinning of the outer nuclear layer and disruption of the photoreceptor layer and retinal pigment epithelium (RPE).\u003c/p\u003e\u003cp\u003eOn the other hand, paracentral acute middle maculopathy (PAMM) is an OCT finding associated with vaso-occlusive retinal conditions of both arterial and venous origin.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Initially classified as a variant of AMN, OCT imaging enabled its differentiation based on distinct features, such as the hyperreflectivity of the inner nuclear layer (INL), which subsequently results in thinning of the INL. This distinction has led to the classification of PAMM as a separate clinical entity from AMN. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Although AMN and PAMM are distinct conditions, they share overlapping characteristics, especially with regard to their presumed ischemic etiology. Furthermore, PAMM and AMN can coexist within the same eye, suggesting a common pathophysiologic mechanism.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNumerous studies utilizing OCT angiography (OCTA) have provided strong evidence that the deep capillary plexus (DCP) is the primary site of damage in PAMM, with associated reductions in vascular flow.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Conversely, the precise localization of ischemic insult in AMN remains a subject of ongoing debate. Historically, capillary flow deficit at the level of the DCP was considered the primary pathogenic mechanism in AMN.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e However, over the past years, increasing attention has shifted toward alterations in the choriocapillaris (CC).\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Recently, Hashimoto et al. reported a single case of bilateral AMN in a 15-year-old male, characterized by an increase in subfoveal choroidal thickness (SFCT) and alterations in choroidal circulation during the acute phase of the disease. These findings resolved over time, supporting the hypothesis of an involvement of the choroidal vasculature. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Also, von der Burchard et al. identified a perfusion deficit in the CC and choroidal layer in AMN, suggesting that choroidal hypoperfusion, rather than the previously believed hypoperfusion of the deep capillary plexus (DCP), is the primary mechanism underlying AMN. However, the study lacked longitudinal assessment of patients before and after resolution of the acute event, and they did not include OCT parameters such as choroidal thickness or the choroidal vascularity index (CVI).\u003c/p\u003e\u003cp\u003eTherefore, the present study aimed to assess the changes in the choroidal vasculature in AMN by quantifying the choroidal thickness and the CVI in the acute phase and after resolution of the disease. To improve measurement accuracy, we used a previously validated artificial intelligence (AI)-based software. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e In addition, we sought to compare these findings with a cohort of PAMM cases to further refine the distinction between these two clinical entities.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e\u003cem\u003eStudy Population\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThis retrospective, observational, multicentric study included patients diagnosed with PAMM and AMN lesions, based on clinical examination and OCT findings. Patients were recruited from the Unit of Ophthalmology, IRCCS University of Bologna (Bologna, Italy) and from the Department of Ophthalmology, IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy). Institutional review board approval was obtained from the respective referral centers for the retrospective chart review. The study adhered to the principles of the Declaration of Helsinki, and all participants provided written informed consent. Diagnostic criteria for acute AMN included the presence of an acute paracentral scotoma corresponding to hyperreflective lesions in the outer retina, accompanied by disruption of the ellipsoid zone (EZ). For PAMM, diagnostic criteria involved a recent history of acute paracentral scotomas, with or without deep intraretinal whitening on fundus examination, hyporeflective wedge-shaped lesions on near infrared reflectance (NIR) imaging, and corresponding hyperreflective lesions in the INL on OCT, as previously described.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Resolution of the acute phase was considered at least 3 months after the event, with the disappearance of acute signs on OCT scans. Exclusion criteria were significant media opacities, other macular conditions (e.g., intermediate or late-stage age-related macular degeneration or diabetic macular edema), poor-quality imaging, any prior ocular surgeries (except cataract surgery), and high myopia. A cohort of healthy age-matched controls was also included, following the same exclusion criteria.\u003c/p\u003e\u003cp\u003e\u003cem\u003eOphthalmological Assessment\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAt baseline and follow-up visits after disease resolution, a comprehensive ophthalmological examination was performed, which included measurement of BCVA, slit-lamp biomicroscopy, intraocular pressure (IOP) assessment, dilated fundus examination using a 90D indirect lens, and spectral-domain (SD)-OCT imaging (Spectralis HRA-OCT; Heidelberg Engineering GmbH, Heidelberg, Germany). BCVA was assessed using a Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis.\u003c/p\u003e\u003cp\u003e\u003cem\u003eOCT Image Acquisition\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAll subjects underwent the same SD-OCT protocol using the Heidelberg Spectralis (Heidelberg Engineering, Germany), which included a dense 20\u0026deg; x 15\u0026deg; raster scan with 145 B-scans spaced 30 \u0026micro;m apart, along with two vertical and horizontal single scans centered on the fovea (with automatic real-time values of at least 14 or higher). OCTA using Carl Zeiss Meditec (Optovue Inc., Fremont, California, USA) or Heidelberg Spectralis was performed when available. Registered and tracked OCT scans from the first and last available visits were obtained for each patient. The subfoveal choroidal thickness (SFCT) was manually measured as the vertical distance between the hyperreflective line of the Bruch membrane and the inner scleral surface using the caliper tool in the image analysis software. Measurements were performed by two independent observers (E.M, M.E.), with discrepancies resolved by a third observer (M.M.).\u003c/p\u003e\u003cp\u003e\u003cem\u003eChoroidal Vascularity Index analysis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo assess the CVI, SD-OCT (Heidelberg Engineering, Heidelberg, Germany) images were used. OCT scans were performed between 9:00 AM and 12:00 PM to minimize diurnal variation effects on choroidal parameters. Registered and tracked OCT scans were used to assess the choroidal vasculature at baseline and after resolution. CVI was measured using an AI-based automated algorithm that included shadow compensation, denoising, localization of the inner and outer choroidal boundaries, and segmentation of the choroidal region from the rest of the scan. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Binarization of the choroid generated bright regions labeled as stromal choroidal areas (SCA) and dark regions labeled as luminal choroidal areas (LCA). CVI was calculated as the ratio of the luminal choroidal area to the total choroidal area (TCA). See Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eGiven the small sample sizes and the non-normal distribution of the data, non-parametric tests were employed. As variables were not normally distributed, they were reported as medians with interquartile ranges (IQR). Fisher\u0026rsquo;s exact test was used to assess associations between categorical variables. The Kruskal-Wallis test was applied to compare choroidal biomarkers among the three groups, and pairwise comparisons using the Dunn-Bonferroni approach were performed for significant variables. The Wilcoxon signed-rank test was used to compare choroidal biomarkers at baseline and after disease resolution. Mann-Whitney U tests were performed to compare AMN with healthy controls, PAMM with healthy controls, and PAMM with AMN eyes. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics version 26.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eDemographic data\u003c/em\u003e\u003c/p\u003e\u003cp\u003eA total of 20 eyes of 20 patients were included in the analysis, 5 eyes with AMN, and 15 eyes with PAMM. Also, 30 eyes of 30 healthy age-matched controls were included in the analysis. Demographics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic data and choroidal biomarkers in acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAMM), and healthy age-matched controls.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControls\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePAMM\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAMN\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, median\u0026thinsp;\u0026plusmn;\u0026thinsp;IQR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e51 (28\u0026ndash;65.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56 (48\u0026ndash;68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46 (29 -48.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex female, number (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (46.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.328\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e280.5 (231-352.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e277 (217.75\u0026ndash;334)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e520 (348.5\u0026ndash;573.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.55 (1.28\u0026ndash;1.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.67 (1.22\u0026ndash;1.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.69 (2.23\u0026ndash;3.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.58 (0.48\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.66 (0.46\u0026ndash;0.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.01 (0.92\u0026ndash;1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.76\u0026ndash;1.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97 (0.76\u0026ndash;1.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.67 (1.30\u0026ndash;2.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e62 (59.75-65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62 (58\u0026ndash;63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62 (58.5\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.605\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSFCT\u0026thinsp;=\u0026thinsp;subfoveal choroidal thickness, TCA\u0026thinsp;=\u0026thinsp;total choroidal area, SCA\u0026thinsp;=\u0026thinsp;stromal choroidal area, LCA\u0026thinsp;=\u0026thinsp;luminal choroidal area, CVI\u0026thinsp;=\u0026thinsp;choroidal vascularity index, IQR\u0026thinsp;=\u0026thinsp;interquartile range.\u003c/p\u003e\u003cp\u003eNo differences in terms of age and sex were observed between the three groups. Median visual acuity was 0.1 LogMar (IQR\u0026thinsp;=\u0026thinsp;0.05\u0026ndash;0.2) in the AMN group and 0.6 LogMar (IQR\u0026thinsp;=\u0026thinsp;0.2\u0026ndash;0.8) in the PAMM group. In the AMN group, one patient underwent a previous bone marrow transplant for acute myeloid leukemia, and one patient had a previous flu-like illness. The remaining three patients did not present concomitant comorbidities at the time of the acute event. In the PAMM group, 5 patients had a concomitant branch retinal artery occlusion (BRAO), 2 patients had concomitant central retinal artery occlusion (CRAO), 3 patients had central retinal vein occlusion (CRVO), and 1 patient branch retinal vein occlusion (BRVO). The remaining 4 patients presented isolated PAMM. Among these patients, two did not have any concomitant comorbidities, one patient had a history of ischemic stroke, and one patient had a homolateral carotid artery stenosis.\u003c/p\u003e\u003cp\u003e\u003cem\u003eChoroidal parameters in AMN, PAMM, and healthy age-matched controls\u003c/em\u003e\u003c/p\u003e\u003cp\u003eEyes with AMN presented an increased SFCT, TCA, SCA, and LCA compared to PAMM and controls. After Dunn-Bonferroni correction, TCA, SCA, and LCA remained statistically significant when comparing AMN and PAMM (p\u0026thinsp;=\u0026thinsp;0.010, p\u0026thinsp;=\u0026thinsp;0.004, p\u0026thinsp;=\u0026thinsp;0.011 respectively), and when comparing AMN and age-matched controls (p\u0026thinsp;=\u0026thinsp;0.006, p\u0026thinsp;=\u0026thinsp;0.016, p\u0026thinsp;=\u0026thinsp;0.012 respectively). On the other hand, SFCT was significantly increased in AMN eyes compared to PAMM (p\u0026thinsp;=\u0026thinsp;0.046), and it was close to significance when comparing AMN to healthy age-matched controls (p\u0026thinsp;=\u0026thinsp;0.056). No significant differences in CVI were observed among the three groups. See Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eChoroidal parameters after resolution\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAfter a median follow-up of 35.52 weeks (range 12\u0026ndash;46 weeks), BCVA improved to 0 (IQR\u0026thinsp;=\u0026thinsp;0-0.05) LogMar in the AMN group and to 0.3 (IQR\u0026thinsp;=\u0026thinsp;0.1\u0026ndash;0.6) LogMar in the PAMM group. SFCT, TCA, SCA, and LCA significantly decreased in AMN eyes. Choroidal thickness reduction after resolution of the acute event was observed in 100% of our cases in the AMN group. CVI presented a slight decrease that did not reach statistical significance. Also, PAMM eyes presented a reduction in SFCT, TCA, SCA, LCA, and CVI, even though the results were not statistically significant. \u003cb\u003eS\u003c/b\u003eee Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComparison of choroidal parameters after resolution in acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAMM), and healthy age-matched controls.\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eResolution\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAcute macular neuroretinopathy (AMN)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e520 (348.5\u0026ndash;573.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e432 (254.5-481.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.043\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.69 (2.23\u0026ndash;3.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.91 (1.75\u0026ndash;2.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.040\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.92\u0026ndash;1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.81 (0.65\u0026ndash;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.040\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.67 (1.30\u0026ndash;2.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.19 (1.04\u0026ndash;1.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.040\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (58.5\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (58-63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eParacentral acute middle maculopathy (PAMM)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e277 (217.75\u0026ndash;334)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e260 (212.5\u0026ndash;345)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.67 (1.22\u0026ndash;1.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.49 (1.16\u0026ndash;2.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.629\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.66 (0.46\u0026ndash;0.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55 (0.45\u0026ndash;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.394\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.97 (0.76\u0026ndash;1.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.83 (0.71-1-27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.551\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (58\u0026ndash;63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (0.59\u0026ndash;0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIQR\u0026thinsp;=\u0026thinsp;interquartile range, SFCT\u0026thinsp;=\u0026thinsp;subfoveal choroidal thickness, TCA\u0026thinsp;=\u0026thinsp;total choroidal area, SCA\u0026thinsp;=\u0026thinsp;stromal choroidal area, LCA\u0026thinsp;=\u0026thinsp;luminal choroidal area, CVI\u0026thinsp;=\u0026thinsp;choroidal vascularity index.\u003c/p\u003e\u003cp\u003eRepresentative cases are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWhen comparing eyes with resolved AMN to healthy age-matched controls, we observed an increase in SFCT, TCA, SCA, and LCA, whereas no changes were observed for CVI. Also, AMN eyes showed a significant increase in SFCT, TCA, SCA and LCA compared to PAMM eyes. Conversely, PAMM eyes presented lower values of SFCT, TCA, SCA, LCA, and CVI compared to healthy controls, but the results were not statistically significant. See Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComparison of choroidal parameters in resolved acute macular neuroretinopathy (AMN), resolved paracentral acute middle maculopathy (PAMM), and healthy controls.\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControls\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eResolved AMN\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e280.5 (231-352.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e432 (254.5-481.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.55 (1.28\u0026ndash;1.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.91 (1.75\u0026ndash;2.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.58 (0.48\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.81 (0.65\u0026ndash;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.76\u0026ndash;1.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.19 (1.04\u0026ndash;1.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.048\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (59.75-65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (58-63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.395\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControls\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eResolved PAMM\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e280.5 (231-352.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e260 (212.5\u0026ndash;345)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.500\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.55 (1.28\u0026ndash;1.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.49 (1.16\u0026ndash;2.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.630\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.58 (0.48\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55 (0.45\u0026ndash;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.885\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.76\u0026ndash;1.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.83 (0.71-1-27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.647\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (59.75-65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (0.59\u0026ndash;0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.537\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResolved AMN\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eResolved PAMM\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSFCT, \u0026#120583;m median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e432 (254.5-481.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e260 (212.5\u0026ndash;345)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.91 (1.75\u0026ndash;2.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.49 (1.16\u0026ndash;2.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.81 (0.65\u0026ndash;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55 (0.45\u0026ndash;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLCA, mm2 median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.19 (1.04\u0026ndash;1.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.83 (0.71-1-27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVI, % median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (58-63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (0.59\u0026ndash;0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.347\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSFCT\u0026thinsp;=\u0026thinsp;subfoveal choroidal thickness, TCA\u0026thinsp;=\u0026thinsp;total choroidal area, SCA\u0026thinsp;=\u0026thinsp;stromal choroidal area, LCA\u0026thinsp;=\u0026thinsp;luminal choroidal area, CVI\u0026thinsp;=\u0026thinsp;choroidal vascularity index, IQR\u0026thinsp;=\u0026thinsp;interquartile range.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, eyes with AMN presented an increased choroidal thickness compared to healthy eyes and PAMM. Also, AMN eyes showed a significant reduction of the choroidal thickness after resolution. On the other hand, we did not observe any significant differences in choroidal parameters in PAMM eyes before and after resolution. Furthermore, choroidal thickness was consistently increased in AMN eyes compared to healthy and PAMM eyes even after resolution.\u003c/p\u003e\u003cp\u003eSeveral studies suggested that PAMM is the result of INL infarction due to vascular impairment occurring at the DCP. \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e In contrast, controversy still exists regarding the pathogenesis of AMN. Pecen et al. and Nemiroff et al. demonstrated capillary flow impairment at the level of the DCP in AMN. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Dansingani and Freund suggested that the perfusion deficit in AMN at the level of the DCP may not be severe enough to cause the typical alterations seen in PAMM. Instead, the characteristic changes at the photoreceptor level are likely a consequence of an ischemic event at the level of the CC.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Thanos and associates supported the theory that AMN may result from a vascular insult in the CC. \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Furthermore, Lee et al. presented a case series of seven AMN patients, where OCTA imaging revealed flow deficits at the CC level during the acute phase of the disease. These perfusion abnormalities were correlated with the characteristic lesions observed on infrared imaging and, at the histological level, with the honeycomb-like microstructure of the choriocapillaris.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Recently, Duan et al. observed a topographic correlation between the neuroretinal lesions characteristic of AMN and the watershed zones at the choroidal level or areas of delayed choroidal perfusion, suggesting that increased vulnerability to hypoperfusion events may result from the presence of a double watershed zone, one between the DCP and the CC and the other at the choroidal watershed zones themselves. \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Again, Hashimoto et al. described the case of a patient in which the choroid at the macula thickened at the onset of AMN and became thin with the regression of disease, suggesting that eyes with AMN may have blood flow impairments at the level of not only the CC but also the choroidal deeper layers. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Consistent with these studies, our findings indicate that choroidal thickness increases in AMN and decreases following the resolution of the acute event, whereas eyes with PAMM did not show significant changes in the choroidal vasculature. These results support the hypothesis that choroidal involvement occurs in AMN but not in PAMM, suggesting distinct pathophysiological mechanisms between the two conditions.\u003c/p\u003e\u003cp\u003eAs previously described, ocular pathologies characterized by an inflammatory process at the choroidal level show choroidal thickening during the acute phases, which then, in the remission phase, results in a reduction of the choroidal thickness. \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Mrejen et al. reported an increase in choroidal thickness in acute posterior multifocal placoid pigment epitheliopathy (APMPPE), which subsequently decreased following resolution of the disease, suggesting that a transient ischemic choroiditis may contribute to secondary damage of the RPE. \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Pellegrini et al. observed an increase in choroidal thickness, TCA, and CVI in eyes with multiple evanescent white dots syndrome (MEWDS), with these choroidal alterations being transient, suggesting that the observed increase in the vascular component is likely due to vascular stasis associated with the inflammatory process.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e In our study, we observed an increase in SFCT, TCA, SCA, and LCA in AMN, supporting the hypothesis that an active inflammatory process might occur in the choroid during the acute phase. However, the CVI value remained unchanged, which may be due to a concurrent increase in both the vascular component, resulting from vascular stasis, and the stromal component, leading to no significant alteration in the CVI. It is noteworthy that in resolved cases of AMN, choroidal biomarkers remained significantly elevated compared to the control group. To the best of our knowledge, this is the first study to report such a finding. These results support the hypothesis of lasting alterations in both the choroidal vascular and stromal components following the acute inflammatory process in AMN.\u003c/p\u003e\u003cp\u003eThe main limitation of this study is the small patient cohort. Therefore, a larger sample size is needed to more effectively compare choroidal changes between AMN, PAMM, and healthy controls. Additionally, the relatively short follow-up period may not capture long-term changes; thus, extended follow-up is necessary to assess the lasting effects on choroidal vasculature in AMN and PAMM. Another limitation is the absence of OCTA images for all study participants, which prevented the analysis of the choriocapillaris (CC). Future research should incorporate multimodal imaging to correlate the CVI with OCTA parameters for a more comprehensive analysis.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study demonstrated an increase in choroidal thickness in AMN, which subsequently decreased following resolution. Also, eyes with AMN presented an increased choroidal thickness compared to healthy controls even after resolution, suggesting that choroidal alterations persist after recovery. On the other hand, no significant changes in choroidal parameters were observed in eyes with PAMM. These findings lend support to the hypothesis that AMN may primarily result from choroidal alterations, suggesting distinct pathophysiological mechanisms compared to PAMM. Further investigations are warranted to determine whether ischemic processes alone are responsible for the condition or if inflammatory mechanisms contribute to its development.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study adhered to the principles of the Declaration of Helsinki, and all participants provided written informed consent and agreed to participate in the study. This study was approved by the Ethics Committee of Bologna, Italy (Cod CE: 53/2025/Oss/AOUBo).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eAll participants have given written permission to publish personal data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u0026nbsp;\u003c/strong\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributorship Statement:\u0026nbsp;\u003c/strong\u003eValsecchi N., Elifani M., Mete M., Maggio E., and Veronese C.conceived and designed the study. Valsecchi N., Elifani M., Maggio E., and Vupparaboina K. K.\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eacquired, analyzed, and interpreted the data\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eValsecchi N.performed statistical analysis.Valsecchi N. and Elifani M. drafted the article.Mete M., Veronese C., Maggio E., Moramarco A., Fontana L., Chhablani J., and Pertile G.\u003cstrong\u003e.\u003c/strong\u003e revised it for intellectual content\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eThe final version of the manuscript was approved by all the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther Acknowledgments:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBos PJM, Deutman AF. Acute Macular Neuroretinopathy. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 1975;80(4):573-584. doi:10.1016/0002-9394(75)90387-6\u003c/li\u003e\n\u003cli\u003eAzar G, Bonnin S, Vasseur V, et al. Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy? \u003cem\u003eJ Clin Med\u003c/em\u003e. 2021;10(21):5038. doi:10.3390/jcm10215038\u003c/li\u003e\n\u003cli\u003eMiller MH, Spalton DJ, Fitzke FW, Bird AC. Acute macular neuroretinopathy. \u003cem\u003eOphthalmology\u003c/em\u003e. 1989;96(2):265-269. doi:10.1016/s0161-6420(89)32906-x\u003c/li\u003e\n\u003cli\u003eBhavsar KV, Lin S, Rahimy E, et al. Acute macular neuroretinopathy: A comprehensive review of the literature. \u003cem\u003eSurv Ophthalmol\u003c/em\u003e. 2016;61(5):538-565. doi:10.1016/j.survophthal.2016.03.003\u003c/li\u003e\n\u003cli\u003eFawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. \u003cem\u003eRetina Phila Pa\u003c/em\u003e. 2012;32(8):1500-1513. doi:10.1097/IAE.0b013e318263d0c3\u003c/li\u003e\n\u003cli\u003eMoura-Coelho N, Gaspar T, Ferreira JT, Dutra-Medeiros M, Cunha JP. Paracentral acute middle maculopathy-review of the literature. \u003cem\u003eGraefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol\u003c/em\u003e. 2020;258(12):2583-2596. doi:10.1007/s00417-020-04826-1\u003c/li\u003e\n\u003cli\u003eSarraf D, Rahimy E, Fawzi AA, et al. Paracentral Acute Middle Maculopathy: A New Variant of Acute Macular Neuroretinopathy Associated With Retinal Capillary Ischemia. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2013;131(10):1275. doi:10.1001/jamaophthalmol.2013.4056\u003c/li\u003e\n\u003cli\u003eIovino C, Au A, Ramtohul P, et al. Coincident PAMM and AMN and Insights Into a Common Pathophysiology. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2022;236:136-146. doi:10.1016/j.ajo.2021.07.004\u003c/li\u003e\n\u003cli\u003eShah A, Rishi P, Chendilnathan C, Kumari S. OCT angiography features of paracentral acute middle maculopathy. \u003cem\u003eIndian J Ophthalmol\u003c/em\u003e. 2019;67(3):417-419. doi:10.4103/ijo.IJO_1249_18\u003c/li\u003e\n\u003cli\u003eCasalino G, Williams M, McAvoy C, Bandello F, Chakravarthy U. Optical coherence tomography angiography in paracentral acute middle maculopathy secondary to central retinal vein occlusion. \u003cem\u003eEye\u003c/em\u003e. 2016;30(6):888-893. doi:10.1038/eye.2016.57\u003c/li\u003e\n\u003cli\u003eRahimy E, Sarraf D. Paracentral acute middle maculopathy spectral-domain optical coherence tomography feature of deep capillary ischemia. \u003cem\u003eCurr Opin Ophthalmol\u003c/em\u003e. 2014;25(3):207-212. doi:10.1097/ICU.0000000000000045\u003c/li\u003e\n\u003cli\u003eRahimy E, Kuehlewein L, Sadda SR, Sarraf D. Paracentral Acute Middle Maculopathy: What We Knew Then and What We Know Now. \u003cem\u003eRetina Phila Pa\u003c/em\u003e. 2015;35(10):1921-1930. doi:10.1097/IAE.0000000000000785\u003c/li\u003e\n\u003cli\u003eThanos A, Faia LJ, Yonekawa Y, Randhawa S. Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2016;134(11):1310-1314. doi:10.1001/jamaophthalmol.2016.3513\u003c/li\u003e\n\u003cli\u003eLee SY, Cheng JL, Gehrs KM, et al. Choroidal Features of Acute Macular Neuroretinopathy via Optical Coherence Tomography Angiography and Correlation With Serial Multimodal Imaging. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2017;135(11):1177-1183. doi:10.1001/jamaophthalmol.2017.3790\u003c/li\u003e\n\u003cli\u003eHashimoto Y, Saito W, Saito M, Hasegawa Y, Ishida S. Increased thickness and decreased blood flow velocity of the choroid in a patient with acute macular neuroretinopathy. \u003cem\u003eBMC Ophthalmol\u003c/em\u003e. 2019;19(1):109. doi:10.1186/s12886-019-1123-0\u003c/li\u003e\n\u003cli\u003eAgrawal R, Wei X, Goud A, Vupparaboina KK, Jana S, Chhablani J. Influence of scanning area on choroidal vascularity index measurement using optical coherence tomography. \u003cem\u003eActa Ophthalmol (Copenh)\u003c/em\u003e. 2017;95(8):e770-e775. doi:10.1111/aos.13442\u003c/li\u003e\n\u003cli\u003eFumi D, Ruggeri F, Fasciolo D, Antonello E, Burtini G, Abdolrahimzadeh S. Paracentral Acute Middle Maculopathy (PAMM) in Ocular Vascular Diseases\u0026mdash;What We Know and Future Perspectives. \u003cem\u003eVision\u003c/em\u003e. 2025;9(1):19. doi:10.3390/vision9010019\u003c/li\u003e\n\u003cli\u003ePecen PE, Smith AG, Ehlers JP. Optical Coherence Tomography Angiography of Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2015;133(12):1478. doi:10.1001/jamaophthalmol.2015.4100\u003c/li\u003e\n\u003cli\u003eNemiroff J, Sarraf D, Davila JP, Rodger D. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF ACUTE MACULAR NEURORETINOPATHY REVEALS DEEP CAPILLARY ISCHEMIA. \u003cem\u003eRetin Cases Brief Rep\u003c/em\u003e. 2018;12(1):S12-S15. doi:10.1097/ICB.0000000000000706\u003c/li\u003e\n\u003cli\u003eDansingani KK, Freund KB. Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy: Related and Distinct Entities. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2015;160(1):1-3.e2. doi:10.1016/j.ajo.2015.05.001\u003c/li\u003e\n\u003cli\u003eThanos A, Faia LJ, Yonekawa Y, Randhawa S. Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2016;134(11):1310. doi:10.1001/jamaophthalmol.2016.3513\u003c/li\u003e\n\u003cli\u003eLee SY, Cheng JL, Gehrs KM, et al. Choroidal Features of Acute Macular Neuroretinopathy via Optical Coherence Tomography Angiography and Correlation With Serial Multimodal Imaging. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2017;135(11):1177. doi:10.1001/jamaophthalmol.2017.3790\u003c/li\u003e\n\u003cli\u003eDuan J, An J, Li M, et al. Topographical Relationship Between Acute Macular Neuroretinopathy and Choroidal Watershed Zone or Patchy Choroidal Filling. \u003cem\u003eFront Med\u003c/em\u003e. 2022;9:762609. doi:10.3389/fmed.2022.762609\u003c/li\u003e\n\u003cli\u003eSteiner M, Esteban-Ortega M del M, Mu\u0026ntilde;oz-Fern\u0026aacute;ndez S. Choroidal and retinal thickness in systemic autoimmune and inflammatory diseases: A review. \u003cem\u003eSurv Ophthalmol\u003c/em\u003e. 2019;64(6):757-769. doi:10.1016/j.survophthal.2019.04.007\u003c/li\u003e\n\u003cli\u003eMrejen S, Sarraf D, Chexal S, Wald K, Freund KB. Choroidal Involvement in Acute Posterior Multifocal Placoid Pigment Epitheliopathy. \u003cem\u003eOphthalmic Surg Lasers Imaging Retina\u003c/em\u003e. 2016;47(1):20-26. doi:10.3928/23258160-20151214-03\u003c/li\u003e\n\u003cli\u003ePellegrini M, Veronese C, Bernabei F, et al. Choroidal Vascular Changes in Multiple Evanescent White Dot Syndrome. \u003cem\u003eOcul Immunol Inflamm\u003c/em\u003e. 2021;29(2):340-345. doi:10.1080/09273948.2019.1678650\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Choroid, AMN, PAMM, pathogenesis","lastPublishedDoi":"10.21203/rs.3.rs-7225320/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7225320/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: To assess choroidal vasculature changes in acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) during the acute and resolution phases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Retrospective, cross-sectional “case-control” comparison study. Twenty eyes from 20 patients were analyzed: 5 with AMN and 15 with PAMM. Also, 30 healthy age-matched controls were included.\u003c/p\u003e\n\u003cp\u003eWe retrospectively analyzed clinical records and spectral-domain optical coherence tomography (SD-OCT) scans from patients affected by AMN and PAMM. Choroidal assessment was performed using an automated algorithm, binarized into stromal choroidal areas (SCA) and luminal choroidal areas (LCA). CVI was calculated as the ratio of LCA to total choroidal area (TCA). Sub-foveal choroidal thickness was measured too. Statistical analysis was done using non-parametric tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Patient’s median age was 52 years (IQR = 30-65.5), and 54% were female. AMN eyes showed significantly increased subfoveal choroidal thickness (SFCT), TCA, SCA, and LCA compared to PAMM and controls (p=0.041, p=0.005, p=0.006, p=0.010 respectively). No significant difference in CVI was observed between the groups (p=0.605). After disease resolution, SFCT, TCA, SCA, and LCA significantly decreased in AMN eyes (p=0.043, p=0.040, p=0.040, p=0.040 respectively), while no changes were observed in PAMM (p\u0026gt;0.05). Also, AMN eyes exhibited higher SFCT, TCA, SCA and LCA compared to controls and PAMM eyes (p\u0026lt;0.05) even after resolution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Increased choroidal thickness is a characteristic feature of AMN, with reduction observed after resolution. On the other hand, no changes in choroidal parameters were observed in PAMM, suggesting distinct pathophysiological mechanisms between the two conditions.\u003c/p\u003e","manuscriptTitle":"Choroidal vascular changes in eyes with acute macular neuroretinopathy and paracentral acute middle maculopathy: new insights","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-17 14:24:35","doi":"10.21203/rs.3.rs-7225320/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-21T09:02:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-20T09:51:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-19T17:56:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18563727968034584891549155482644017875","date":"2026-01-13T12:07:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332395810604174460972220315654246483394","date":"2026-01-12T13:03:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"142315806264193033161676169759701021674","date":"2025-08-10T17:43:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-09T08:42:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-09T08:37:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-04T05:54:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-01T16:54:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-08-01T16:51:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c13bd6f9-a71d-41d1-a7f1-3b01363401a0","owner":[],"postedDate":"August 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:10:52+00:00","versionOfRecord":{"articleIdentity":"rs-7225320","link":"https://doi.org/10.1186/s12886-026-04671-6","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2026-02-11 15:57:51","publishedOnDateReadable":"February 11th, 2026"},"versionCreatedAt":"2025-08-17 14:24:35","video":"","vorDoi":"10.1186/s12886-026-04671-6","vorDoiUrl":"https://doi.org/10.1186/s12886-026-04671-6","workflowStages":[]},"version":"v1","identity":"rs-7225320","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7225320","identity":"rs-7225320","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}