Impact of Retinal Traction Induced by Epiretinal Membrane on Aniseikonia

Impact of Retinal Traction Induced by Epiretinal Membrane on Aniseikonia | 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 Article Impact of Retinal Traction Induced by Epiretinal Membrane on Aniseikonia Masayuki Hirano, Shun Minakawa, Yuta Imamura, Naoko Yamamoto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4439805/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Oct, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract We investigated the effect of retinal traction caused by epiretinal membranes (ERMs) on aniseikonia and retinal microstructures in 81 unilateral ERMs. Retinal traction was quantified by measuring the maximum depth of the retinal fold (MDRF) using en face optical coherence tomography (OCT) images. Measurements included the mean inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), central retinal thickness (CRT), and interocular ratios of the foveal avascular zone (FAZ) area (FAZ ratio). Significant correlations were found between the preoperative MDRF and preoperative aniseikonia ( P < 0.001), INL thickness ( P < 0.001), CRT ( P < 0.001), and FAZ ratio ( P = 0.003). Preoperative aniseikonia was significantly correlated with preoperative INL and OPL-ONL thicknesses ( P < 0.001 and P = 0.020, respectively) and CRT ( P = 0.003). Multiple regression analysis revealed that preoperative aniseikonia was significantly associated with preoperative MDRF, INL, and OPL-ONL thicknesses ( P = 0.029, 0.006, and 0.006, respectively). Twenty-nine eyes underwent membrane peeling, resolving all retinal folds 6 months postoperatively. A significant correlation was observed between preoperative MDRF and postoperative aniseikonia ( P = 0.011). Our findings suggest that retinal traction by ERM is significantly associated with aniseikonia both pre- and postoperatively, alongside other OCT parameters. Health sciences/Medical research Physical sciences/Optics and photonics aniseikonia retina optical coherence tomography epiretinal membrane retinal traction Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction The epiretinal membrane (ERM) is an abnormal fibroproliferative tissue that develops on the internal limiting membrane (ILM) of the retina in the macular region and causes various visual dysfunctions [ 1 – 3 ]. Aniseikonia and metamorphopsia are typical visual impairments associated with ERM [ 4 – 11 ]. Aniseikonia, which affects the quality of vision (QOV), presents symptoms in sensitive individuals, with an aniseikonia ranging from 1–3%. Aniseikonia of ≥ 3% causes binocular impairment, and that of ≥ 5% completely impairs binocular vision [ 12 , 13 ]. Hence, it is critical to develop treatment strategies to prevent ERM-induced aniseikonia from affecting the QOV. Visual dysfunction in patients with ERMs is commonly attributed to retinal traction, yet a quantitative method for evaluating the traction on the retina is lacking. The recent advent of swept-source optical coherence tomography (SS-OCT), with its enhanced penetration and scan speed compared to conventional spectral-domain OCT, has made it possible to capture three-dimensional (3D) images of the retinal structure. Utilizing en face images constructed from these 3D scans, the distribution of ERM on the retinal surface and changes in the retinal structure caused by ERM-induced retinal retraction, such as retinal folds, can be visualized at an arbitrary retinal depth from a bird's-eye view. Furthermore, it is generally known that when folds occur in a thin elastic membrane, the maximum amplitude of folds increases with rising compressive stress [ 14 – 16 ]. Therefore, by measuring the depth of retinal folds using en face images, retinal traction force can be quantitatively evaluated. Specifically, studies have reported that the maximum depth of retinal folds within a 3-mm-diameter circle centered on the macula (MDRF) correlates with metamorphopsia in patients with ERM [ 17 – 22 ]. Despite aniseikonia being a primary contributor to the decline in QOV caused by ERM, there are no reports on the relationship between the percentage of aniseikonia and retinal traction. It is, therefore, necessary to elucidate the association between retinal traction and aniseikonia to understand the strength of traction impacting QOV due to aniseikonia and to apply this knowledge to clinical practice. Secondary changes in retinal structure induced by ERM traction include the thickening of specific retinal layers and a reduction in the foveal avascular zone (FAZ), both correlated with the degree of metamorphopsia and aniseikonia [ 4 – 9 , 23 – 26 ]. However, the mechanisms by which ERM causes these changes remain unclear. Given that retinal traction is a major pathology of ERM, it is necessary to clarify the relationship between retinal traction and these retinal alterations. In this study, we quantified retinal traction in patients with ERMs by measuring the MDRF and examined its relationship with the incidence of aniseikonia. Additionally, we investigated the relationship between MDRF and OCT parameters, such as mean inner nuclear layer (INL) thickness, mean outer plexiform layer (OPL)-outer nuclear layer (ONL) thickness, central retinal thickness (CRT), and intraocular FAZ ratio, all previously reported to be associated with aniseikonia. Furthermore, we investigated the relationship between MDRF and the percentage of postoperative aniseikonia in patients who had undergone surgical ERM resection. Results Relationship Between Pre- and Postoperative Aniseikonia and Preoperative MDRF We examined the relationship between the preoperative mean aniseikonia and the preoperative MDRF. A significant correlation was observed between the mean percentage of preoperative aniseikonia and preoperative MDRF (y = 0.0417x − 0.0757; r = 0.487; P < 0.001; Fig. 1 ). Twenty-nine eyes of 29 patients (15 men and 14 women) with a mean age of 67.5 ± 7.1 years underwent vitrectomy with ERM and ILM peeling, with 22 eyes (75.8%) undergoing simultaneous cataract surgery. No surgical complications occurred during or after surgery in any case. In all cases, retinal folds within a 3-mm-diameter circle centered on the macula were present preoperatively but disappeared by 6 months postoperatively, as illustrated in Fig. 3 . We examined the relationship between the mean percentage of aniseikonia 6 months postoperatively and the preoperative MDRF. The correlation between the mean percentage of aniseikonia at 6 months postoperatively and the preoperative MDRF was also significant (y = 0.0368x − 0.5893; r = 0.467; P = 0.011; Fig. 2 ). According to regression line equations, the preoperative and postoperative MDRF values corresponding to the threshold at which aniseikonia interfered with daily life (aniseikonia of 3%) were 73.75 µm and 97.53 µm, respectively. Relationship Between Preoperative MDRF and Preoperative OCT Parameters The correlation between preoperative MDRF and OCT parameters associated with aniseikonia, such as the mean INL and OPL-ONL thickness, CRT, and intraocular FAZ ratio, was examined. As shown in Fig. 4 , the preoperative MDRF was significantly correlated with the mean preoperative INL thickness (r = 0.562, P < 0.001), preoperative CRT (r = 0.588, P < 0.001), and preoperative FAZ ratio (r = -0.328, P = 0.003), but not with the mean preoperative OPL-ONL thickness (r = 0.214, P = 0.055). Relationship Between Preoperative Aniseikonia and Preoperative OCT Parameters We examined the relationship between the mean percentage of aniseikonia preoperatively and preoperative OCT parameters, such as the mean INL and OPL-ONL thickness, CRT, and intraocular FAZ ratio. As shown in Fig. 5 , the mean percentage of aniseikonia preoperatively significantly correlated with the mean preoperative INL and OPL-ONL thicknesses (r = 0.524, P < 0.001; r = 0.259, P = 0.020; respectively) and preoperative CRT (r = 0.331, P = 0.003), but not with the preoperative FAZ ratio (r = -0.328, P = 0.066). Multiple Regression Analysis for Aniseikonia Multiple regression analysis was conducted with the mean percentage of aniseikonia preoperatively as the dependent variable and preoperative MDRF, mean preoperative INL and OPL-ONL thicknesses, and preoperative CRT as independent variables. As shown in Table 1 , the preoperative MDRF, mean preoperative INL, and OPL-ONL thicknesses were significantly associated with the mean percentage of aniseikonia preoperatively ( P = 0.029, 0.006 and 0.006, respectively). Table 1 Multiple Regression Analysis of Preoperative Aniseikonia. β SE P -value Preoperative MDRF (µm) 0.271 0.013 0.029 Preoperative INL thickness (µm) 0.457 0.457 0.006 Preoperative OPL-ONL thickness (µm) 0.303 0.303 0.006 Central retinal thickness (µm) -0.316 0.009 0.071 Β, standard regression coefficient. INL, inner nuclear layer. MDRF, maximum depth of retinal folds. OPL-ONL, outer plexiform layer-outer nuclear layer. SE, standard error. R 2 = 0.344. Effect of Surgical Removal of ERM and ILM on Visual Functions and En Face Image Findings As shown in Table 2 , significant improvements were noted in the best-corrected visual acuity (BCVA), mean INL thickness, and CRT 6 months postoperatively ( P < 0.001, 0.005, and < 0.001, respectively). However, there was no significant improvement in the mean percentage of aniseikonia ( P = 0.512). A significant increase in the mean OPL-ONL thickness was observed ( P < 0.001). Table 2 Comparison of Preoperative and 6-Month Postoperative Visual Functions and Optical Coherence Tomography Findings. Baseline 6 months postoperatively P- value MRDF (µm) 106.4 ± 41.7 0 < 0.001 Mean aniseikonia 3.89 ± 3.33 3.51 ± 2.71 0.508 LogMAR BCVA 0.10 ± 0.22 -0.06 ± 0.13 < 0.001 INL thickness (µm) 55.2 ± 12.2 50.1 ± 9.30 0.007 OPL-ONL thickness (µm) 101.8 ± 13.6 112.5 ± 12.5 < 0.001 Central retinal thickness (µm) 423.7 ± 79.6 359.8 ± 35.8 < 0.001 FAZ ratio 0.443 ± 0.35 0.393 ± 0.24 0.288 BCVA, best-corrected visual acuity. FAZ, foveal avascular zone. INL, inner nuclear layer. LogMAR, logarithm of the minimum angle of resolution. MDRF, maximum depth of retinal folds. OPL-ONL, outer plexiform layer-outer nuclear layer. Data are presented as mean ± standard deviation unless otherwise indicated. Discussion Our current study revealed, for the first time, that both preoperative and postoperative aniseikonia caused by ERM correlate with preoperative MDRF. These results suggest that MDRF measurements may have clinical applications in determining the timing of surgery. While ERM causes aniseikonia due to retinal traction, mild aniseikonia does not adversely affect daily life. However, aniseikonia causes binocular vision dysfunction in patients with aniseikonia of ≥ 3% and fusion disorder in patients with aniseikonia of ≥ 5% [ 13 ]. Therefore, preventing aniseikonia from reaching 3% is crucial in ERM treatment. Using 3% of aniseikonia as the cutoff, the MDRF value corresponding to 3% was calculated to be 73.7 µm based on the relationship between preoperative MDRF and preoperative aniseikonia (y = 0.047x − 0.0757). Similarly, the MDRF value corresponding to 3% was calculated from the relationship between preoperative MDRF and postoperative aniseikonia (y = 0.0329x + 0.0159) to be 90.7 µm. In other words, the timing of surgical intervention to remove traction when the MDRF is between 73.7 µm and 90.7 µm can be considered before the aniseikonia significantly affects the patient's daily life. Preoperative and postoperative MDRF in ERM have also been reported to correlate with metamorphopsia [ 19 , 23 ]. Kanzaki et al. suggested that surgical treatment should be performed when the MDRF is between 69 µm and 118 µm, using 0.5 as the cutoff for the M-score value at which metamorphopsia affects daily life [ 19 ]. This indicates that the timing of surgical treatment before visual dysfunction due to aniseikonia and metamorphopsia caused by ERM interferes with daily life based on MDRF values, the timing of surgical treatment is considered to have the same level of traction for the prevention of visual function due to inequality and prevention of visual function due to metamorphopsia. The results of this study and the Kanzaki et al. study indicate that even in situations where aniseikonia and M-score cannot be measured in symptomatic patients, measurement of MDRF by OCT imaging can now tell whether a degree of traction has occurred that would require surgery. Additionally to preoperative MDRF, preoperative INL and OPL-ONL thicknesses were significant factors in the multivariate analysis for preoperative aniseikonia. Okamoto et al. reported that INL thickness was a significant factor for aniseikonia due to ERM, whereas OPL-ONL thickness was not a significant factor [ 7 ]. In the present study, the mean aniseikonia, mean INL thickness, and mean OPL-ONL thickness in all patients were 3.1 ± 3.8%, 49 ± 13 µm, and 100 ± 17 µm, respectively, compared to 6.2 ± 4.5%, 104 ± 33 µm, and 196 ± 24 µm, respectively, in Okamoto et al.'s study. The difference may be because the study by Okamoto et al. was limited to ERM cases that had undergone surgery, whereas the present study included mild cases for which surgery was not indicated. Thus, in addition to MDRF and INL thicknesses, OPL-ONL thickness may also influence aniseikonia in patients with mild ERM. This study also revealed a relationship between MDRF and OCT parameters, which have previously been reported to be correlated with aniseikonia caused by ERM. Preoperative MDRF significantly correlated with preoperative INL thickness, preoperative CRT, and preoperative FAZ ratio, but not with preoperative OPL-ONL thickness. Kanzaki et al. also reported that although INL and OPL-ONL thicknesses correlated with MDRF, OPL-ONL thickness did not correlate with the amount of MDRF progression or thickness change over time [ 20 ]. This study revealed that an increase in INL thickness but also CRT and FAZ ratios are secondary structural changes correlating with retinal traction. Furthermore, it appears that OPL-ONL thickness has a weaker relationship with retinal traction compared to other OCT parameters. A more detailed study of the effects of retinal traction on the retinal structure is necessary. In this study, retinal folds were observed in all 29 eyes that had undergone ERM removal surgery preoperatively but had disappeared in all cases 6 months postoperatively. Retinal folds occur due to tangential traction applied to the retina [ 14 – 16 ]. Therefore, their disappearance indicates that the traction applied to the retina was released. However, no significant improvement in aniseikonia was observed postoperatively despite traction removal. Regarding whether aniseikonia improves with surgical intervention in patients with ERM, although there are some reports of significant improvement [ 23 , 27 ], others report no improvement [ 7 , 10 ]. ERM may cause aniseikonia by altering the distribution of Müller cells and photoreceptor cells due to traction, with no postoperative improvement attributed to the unchanged cell distribution [ 7 , 28 ]. This appears consistent even in cases where the traction was completely removed by surgical intervention, and all retinal folds disappeared, as in the present surgical cases. Detailed studies are needed to examine the effects of ERM traction and the surgical removal of the traction on aniseikonia. The limitations of this study include its retrospective design, small sample size, and relatively short follow-up period. Additionally, factors other than MDRF, such as retinal fold parameters (i.e., number, distribution pattern, and duration of folds), ERM components, and age-related retinal characteristics, may contribute to visual impairment in ERM. Therefore, further investigations are warranted. In conclusion, retinal traction quantified by MDRF correlates with aniseikonia, and surgery to remove retinal traction at MDRF values between 73.7 µm and 90.7 µm may prevent QOV reduction due to aniseikonia. Methods Study Design and Ethical Considerations This was a retrospective, consecutive observational study. All investigative procedures adhered to the principles outlined in the tenets of the Declaration of Helsinki. The study was approved by the Ethics Committee of the Himeji Red Cross Hospital, Hyogo, Japan (approval no: 2022-23). Informed consent was obtained using an opt-out procedure. Subjects We retrospectively reviewed the charts of a consecutive series of 81 eyes of 81 patients with unilateral idiopathic ERM who visited the Himeji Red Cross Hospital between February 1, 2019 and January 31, 2023. Patients with a history of other retinal diseases, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, uveitis, and anisometropia > 1 dpt, as well as those who had undergone vitreoretinal surgery, were excluded. Ophthalmic Examinations All patients underwent comprehensive ophthalmologic examinations before and 6 months after surgery, including BCVA testing with refraction using a 5-m Landolt C acuity chart, indirect and contact lens slit-lamp biomicroscopy, and SS-OCT (DRI OCT-1 Triton; Topcon Corporation, Tokyo, Japan). Quantification of aniseikonia The New Aniseikonia Test (NAT; Handaya, Tokyo, Japan) was utilized to quantify the severity of aniseikonia. This test consists of a book and spectacles and measures aniseikonia by separating binocular vision with red and green filters. Each eye perceives a half-moon printed on a book page. Two half-moons of different sizes in each pair were arranged in series, with the difference varying in increments of 1%. The subjects wore red-green spectacles and viewed the plates to allow the right eye to see one of the half-moons in each pair and the left eye to see the other half-moon. The participants indicated the pair in which the two half-moons appeared to be of equal size. The actual size difference between the half-moons in the pair represented the percentage of the subject's aniseikonia. The NAT target size was 4 cm (visual field angle, 5.7°), and measurements ranging from 1–24% were possible. Measurements were done at approximately 40 cm along both the vertical and horizontal meridians, and their mean values were used for data analysis. SS-OCT and En Face Imaging SS-OCT images were captured in both B-scan and 3D modes (3 × 3-mm area consisting of 320 × 320 A-scans and 6 × 6-mm area consisting of 512 × 512 A-scans); image analysis software, IMAGEnet6, Version 1.22 (Topcon Corporation, Tokyo, Japan), was used for en face and OCT angiography (OCTA) image construction. Based on the retinal layer boundary information, IMAGEnet6 aligned the 3D-OCT volume scan data along a specific retinal layer boundary, generating en face and OCTA images at an arbitrary depth. Additionally, CRT measurements were obtained at the fovea within a 1-mm-diameter circle using the built-in calculation system of the SS-OCT. Measurement of MDRF MDRF was measured within a 3-mm-diameter circle centered at the fovea as previously described [ 17 – 19 ]. The 3D OCT volume scan data were flattened at the level of the ILM to visualize the black lines corresponding to the retinal folds due to retinal traction by ERM on the en face image below the ILM level. We then measured the slab depth of the en face image, in which the black lines corresponding to the deepest retinal folds disappeared within the parafoveal area (Fig. 6 ). Measurement of the FAZ Area and the Interocular Ratios of the FAZ Area Superficial capillary plexus (SCP) en face images from 3 × 3-mm OCTA images were used to measure the FAZ area in both eyes with the ERM and fellow eyes. The en face images of the SCP were constructed from the data 2.6 µm below the ILM and 15.6 µm below the inner plexiform layer. FAZ contour in the SCP was manually traced, and IMAGEnet6 automatically computed the surface area within the drawing-in contour. The interocular ratio of the FAZ area in the ERM eyes to that in the fellow eyes was calculated (Supplementary Fig. S1 ). Measurement of the Mean INL and ONL-OPL Thicknesses B-scan OCT images of the vertical and horizontal cross-sections through the fovea were used to measure mean INL and ONL-OPL thicknesses. Measurements were obtained from points located 500 µm and 1000 µm away from the fovea in the superior, inferior, nasal, and temporal regions (1 point at 500 µm and 1 at 1000 µm in each of the four regions; total 8 points; Supplementary Fig. S2 ). The average of the eight values was used for statistical analysis. Surgical Procedure Indications for ERM surgery included decreased visual acuity (< 20/20) or complaints of metamorphopsia or aniseikonia. All patients provided written informed consent preoperatively after the risks and benefits of all surgical procedures were explained to them. In all eyes, triamcinolone acetonide was used intraoperatively to facilitate the visualization of the vitreous and posterior hyaloid. After core vitrectomy using a 27-gauge microincision vitrectomy system (Constellation; Alcon Laboratories, Inc., Fort Worth, Texas, USA), the ERM and ILM were removed using end-gripping forceps. ILM peeling was performed after staining with 0.25 mg/mL brilliant blue G solution (Coonassie BBG 250; Sigma-Aldrich, St. Louis, Missouri, USA). Cataract extraction with posterior chamber intraocular lens implantation was performed before pars plana vitrectomy in all cataract cases. All the surgeries were performed by a single surgeon (M. H.). Statistical Analysis All data ware expressed the mean ± standard deviation. BCVAs were recorded as decimal values and converted to the logarithm of the minimum angle of resolution (logMAR) units for statistical analysis. Visual acuity results were presented as logMAR units and Snellen visual acuities. Statistical analyses were conducted using SPSS, version 24.0.0.0 (IBM Corporation, Armonk, New York, USA). Spearman rank correlation tests were used to assess relationships between the mean percentage of aniseikonia and MDRF, mean INL and ONL-OPL thicknesses, CRT, and FAZ ratio. The relationships between MDRF and the mean INL and ONL-OPL thicknesses, CRT, and FAZ ratio were also analyzed using Spearman rank correlation tests. The mean aniseikonia, mean INL and ONL-OPL thicknesses, and CRT and FAZ ratios before and 6 months after surgery were compared using the Wilcoxon signed-rank test. A P -value of < 0.05 was considered to be statistically significant. Data availability statement Data supporting the findings of this study are available from the corresponding author, M.H., upon reasonable request. Declarations Additional information The authors report no competing interests. Author Contribution M.H. designed and conducted the study. M.H., S.M., Y.I., and N.Y. collected the data. M.H. managed, analyzed, and interpreted the data and wrote the article. 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Supplementary Files SupplementaryFigureLegends.docx SupplementaryFigureS1.tif SupplementaryFigureS2.tif Cite Share Download PDF Status: Published Journal Publication published 23 Oct, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 22 Jul, 2024 Reviews received at journal 21 Jul, 2024 Reviews received at journal 17 Jul, 2024 Reviewers agreed at journal 16 Jul, 2024 Reviewers agreed at journal 15 Jul, 2024 Reviewers invited by journal 15 Jul, 2024 Editor assigned by journal 15 Jul, 2024 Editor invited by journal 22 May, 2024 Submission checks completed at journal 22 May, 2024 First submitted to journal 18 May, 2024 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-4439805","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":309470622,"identity":"32b16d0a-6260-4ed8-b7c9-46b750d4ad41","order_by":0,"name":"Masayuki Hirano","email":"data:image/png;base64,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","orcid":"","institution":"Himeji Red Cross Hospital","correspondingAuthor":true,"prefix":"","firstName":"Masayuki","middleName":"","lastName":"Hirano","suffix":""},{"id":309470624,"identity":"f0cfe7f8-7cf2-47a1-b56a-bdffa2ed14a6","order_by":1,"name":"Shun Minakawa","email":"","orcid":"","institution":"Himeji Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shun","middleName":"","lastName":"Minakawa","suffix":""},{"id":309470625,"identity":"e5c53e55-ae40-414a-bb91-64ef65d3fac3","order_by":2,"name":"Yuta Imamura","email":"","orcid":"","institution":"Himeji Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Imamura","suffix":""},{"id":309470628,"identity":"84a5a539-1225-4110-8e38-69b323dc33e1","order_by":3,"name":"Naoko Yamamoto","email":"","orcid":"","institution":"Himeji Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Naoko","middleName":"","lastName":"Yamamoto","suffix":""}],"badges":[],"createdAt":"2024-05-18 06:54:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4439805/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4439805/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-72048-0","type":"published","date":"2024-10-23T15:58:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":57875159,"identity":"c9246816-42db-436c-8eeb-3bc7ff9d8a23","added_by":"auto","created_at":"2024-06-06 18:53:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":245221,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the preoperative maximum depth of the retinal fold (MDRF) and mean preoperative aniseikonia.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/969c0ae18c7a8b3eec18f7ae.png"},{"id":57874263,"identity":"673d11cf-a6ec-41be-b792-c297699f8705","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":219567,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between preoperative MDRF and the mean percentage of aniseikonia 6 months postoperatively.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/a985d7faa3ecb18f9c7738e2.png"},{"id":57874266,"identity":"20f8799d-e11e-45ed-b835-288c97ed0beb","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4021608,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative images from a 64-year-old man (\u003cstrong\u003ea\u003c/strong\u003e–\u003cstrong\u003ec\u003c/strong\u003e) before and (\u003cstrong\u003ed\u003c/strong\u003e–\u003cstrong\u003ef\u003c/strong\u003e) 6 months after epiretinal membrane (ERM) surgery. En face images at the (\u003cstrong\u003ea\u003c/strong\u003e, \u003cstrong\u003ed\u003c/strong\u003e) internal limiting membrane (ILM) level and (\u003cstrong\u003eb\u003c/strong\u003e, \u003cstrong\u003ee\u003c/strong\u003e) 13.0 μm below the ILM are shown. (\u003cstrong\u003ec\u003c/strong\u003e, \u003cstrong\u003ef\u003c/strong\u003e) The white dotted arrows in A and D indicate the scan sections of the B-scan images. The white arrowheads in (\u003cstrong\u003ea\u003c/strong\u003e) and (\u003cstrong\u003ec\u003c/strong\u003e) indicate ERM. (\u003cstrong\u003ea\u003c/strong\u003e) ERM in en face image at the ILM level shows an irregular surface. (\u003cstrong\u003eb\u003c/strong\u003e) Multiple retinal folds, depicted as black linear structures (white arrows), preoperatively are no longer present in (\u003cstrong\u003ee\u003c/strong\u003e) the en face image 6 months postoperatively. The maximum depth of retinal folds preoperatively was 62.4 μm. The mean percentage of aniseikonia before and at 6 months after surgery were +3.0% and +1.0%, respectively. Best-corrected visual acuity (BCVA) before and at 6 months after surgery were 20/20 and 20/12, respectively.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/cc1138f66c66028a3d24ab9f.png"},{"id":57874265,"identity":"c10012b5-a477-47b0-8753-9429cf600056","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":305388,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between preoperative MDRF and optical coherence tomography (OCT) parameters: (\u003cstrong\u003ea\u003c/strong\u003e) mean preoperative inner nuclear layer (INL) thickness, (\u003cstrong\u003eb\u003c/strong\u003e) mean preoperative outer plexiform layer (OPL)-outer nuclear layer (ONL) thickness, (\u003cstrong\u003ec\u003c/strong\u003e) preoperative central retinal thickness (CRT), and (\u003cstrong\u003ed\u003c/strong\u003e) preoperative foveal avascular zone (FAZ) ratio.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/fd0ee53319cbe65acfa9a87f.png"},{"id":57874267,"identity":"0b692943-04dc-4ea6-8c32-f0eb8cef15c1","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":275027,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the mean percentage of preoperative aniseikonia and preoperative OCT parameters: (\u003cstrong\u003ea\u003c/strong\u003e) mean preoperative INL thickness, (\u003cstrong\u003eb\u003c/strong\u003e) mean preoperative OPL-ONL thickness, (\u003cstrong\u003ec\u003c/strong\u003e) preoperative CRT, and (\u003cstrong\u003ed\u003c/strong\u003e) preoperative FAZ ratio.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/d3b25fd9d3cbde11ae018564.png"},{"id":57874270,"identity":"28f95ea8-6ad4-4564-9db3-43eb763a9b26","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":5820051,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative en face images demonstrating the method used to detect the MDRF. En face images (\u003cstrong\u003ea\u003c/strong\u003e, \u003cstrong\u003eb\u003c/strong\u003e) at the ILM level, (\u003cstrong\u003ed\u003c/strong\u003e, \u003cstrong\u003ee\u003c/strong\u003e) 20.0 μm below the ILM, and (\u003cstrong\u003eg\u003c/strong\u003e, \u003cstrong\u003eh\u003c/strong\u003e) 96.2 μm below the ILM, as well as (\u003cstrong\u003ec\u003c/strong\u003e, \u003cstrong\u003ef\u003c/strong\u003e, \u003cstrong\u003ei\u003c/strong\u003e) corresponding B-scan OCT images are shown. (\u003cstrong\u003eb\u003c/strong\u003e, \u003cstrong\u003ee\u003c/strong\u003e, \u003cstrong\u003eh\u003c/strong\u003e) The dotted arrow indicates the location of the B-scan sections. (\u003cstrong\u003ec, f, i\u003c/strong\u003e) The orange lines in (\u003cstrong\u003ec\u003c/strong\u003e), (\u003cstrong\u003ef\u003c/strong\u003e), and (\u003cstrong\u003ei\u003c/strong\u003e) indicate the slabs at which the en face images of (\u003cstrong\u003ea\u003c/strong\u003e) and (\u003cstrong\u003eb\u003c/strong\u003e), (\u003cstrong\u003ed\u003c/strong\u003e) and (\u003cstrong\u003ee\u003c/strong\u003e), and (\u003cstrong\u003eg\u003c/strong\u003e) and (\u003cstrong\u003eh\u003c/strong\u003e) are made. (\u003cstrong\u003ea\u003c/strong\u003e, \u003cstrong\u003eb\u003c/strong\u003e) En face image at the ILM level shows an ERM (indicated by white arrowhead). (\u003cstrong\u003ed\u003c/strong\u003e, \u003cstrong\u003ee\u003c/strong\u003e) En face image at 20.0 μm below the ILM level shows multiple black lines corresponding to retinal folds (white arrows). (\u003cstrong\u003eh\u003c/strong\u003e) The white arrowhead shows the only retinal fold observed in this slab, indicating the MDRF in the parafoveal area. This retinal fold disappeared in the en face images constructed at a deeper level than this image. Therefore, the MDRF in this case was 96.2 μm. (\u003cstrong\u003ei\u003c/strong\u003e) The white arrowhead points to the deepest retinal fold, with the orange line passing through its deepest part.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/6d6a9979c3061664ece11345.png"},{"id":67682048,"identity":"5b56ad0d-087b-4246-aecb-5b5b99598714","added_by":"auto","created_at":"2024-10-28 16:12:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14869400,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/2acdc129-d7d9-4180-85c4-d0dc681f177b.pdf"},{"id":57874271,"identity":"4b969fd8-0d70-43b3-929c-287570c3f8a3","added_by":"auto","created_at":"2024-06-06 18:45:38","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":38753,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureLegends.docx","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/f004313a033f4dc3c5ced95b.docx"},{"id":57874272,"identity":"2a4e698f-249d-4d3c-9ae2-df35f91271e8","added_by":"auto","created_at":"2024-06-06 18:45:39","extension":"tif","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":24625552,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/d93a5e25d3a37ba142f05d09.tif"},{"id":57874273,"identity":"5c221176-970b-4399-a35c-01a087a62966","added_by":"auto","created_at":"2024-06-06 18:45:39","extension":"tif","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":24625540,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS2.tif","url":"https://assets-eu.researchsquare.com/files/rs-4439805/v1/d18e939fc82df1d46751c150.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Retinal Traction Induced by Epiretinal Membrane on Aniseikonia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe epiretinal membrane (ERM) is an abnormal fibroproliferative tissue that develops on the internal limiting membrane (ILM) of the retina in the macular region and causes various visual dysfunctions [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Aniseikonia and metamorphopsia are typical visual impairments associated with ERM [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Aniseikonia, which affects the quality of vision (QOV), presents symptoms in sensitive individuals, with an aniseikonia ranging from 1\u0026ndash;3%. Aniseikonia of \u0026ge;\u0026thinsp;3% causes binocular impairment, and that of \u0026ge;\u0026thinsp;5% completely impairs binocular vision [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Hence, it is critical to develop treatment strategies to prevent ERM-induced aniseikonia from affecting the QOV.\u003c/p\u003e \u003cp\u003eVisual dysfunction in patients with ERMs is commonly attributed to retinal traction, yet a quantitative method for evaluating the traction on the retina is lacking. The recent advent of swept-source optical coherence tomography (SS-OCT), with its enhanced penetration and scan speed compared to conventional spectral-domain OCT, has made it possible to capture three-dimensional (3D) images of the retinal structure. Utilizing en face images constructed from these 3D scans, the distribution of ERM on the retinal surface and changes in the retinal structure caused by ERM-induced retinal retraction, such as retinal folds, can be visualized at an arbitrary retinal depth from a bird's-eye view. Furthermore, it is generally known that when folds occur in a thin elastic membrane, the maximum amplitude of folds increases with rising compressive stress [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, by measuring the depth of retinal folds using en face images, retinal traction force can be quantitatively evaluated. Specifically, studies have reported that the maximum depth of retinal folds within a 3-mm-diameter circle centered on the macula (MDRF) correlates with metamorphopsia in patients with ERM [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Despite aniseikonia being a primary contributor to the decline in QOV caused by ERM, there are no reports on the relationship between the percentage of aniseikonia and retinal traction. It is, therefore, necessary to elucidate the association between retinal traction and aniseikonia to understand the strength of traction impacting QOV due to aniseikonia and to apply this knowledge to clinical practice.\u003c/p\u003e \u003cp\u003eSecondary changes in retinal structure induced by ERM traction include the thickening of specific retinal layers and a reduction in the foveal avascular zone (FAZ), both correlated with the degree of metamorphopsia and aniseikonia [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, the mechanisms by which ERM causes these changes remain unclear. Given that retinal traction is a major pathology of ERM, it is necessary to clarify the relationship between retinal traction and these retinal alterations.\u003c/p\u003e \u003cp\u003eIn this study, we quantified retinal traction in patients with ERMs by measuring the MDRF and examined its relationship with the incidence of aniseikonia. Additionally, we investigated the relationship between MDRF and OCT parameters, such as mean inner nuclear layer (INL) thickness, mean outer plexiform layer (OPL)-outer nuclear layer (ONL) thickness, central retinal thickness (CRT), and intraocular FAZ ratio, all previously reported to be associated with aniseikonia. Furthermore, we investigated the relationship between MDRF and the percentage of postoperative aniseikonia in patients who had undergone surgical ERM resection.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eRelationship Between Pre- and Postoperative Aniseikonia and Preoperative MDRF\u003c/h2\u003e \u003cp\u003eWe examined the relationship between the preoperative mean aniseikonia and the preoperative MDRF. A significant correlation was observed between the mean percentage of preoperative aniseikonia and preoperative MDRF (y\u0026thinsp;=\u0026thinsp;0.0417x \u0026minus;\u0026thinsp;0.0757; r\u0026thinsp;=\u0026thinsp;0.487; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Twenty-nine eyes of 29 patients (15 men and 14 women) with a mean age of 67.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1 years underwent vitrectomy with ERM and ILM peeling, with 22 eyes (75.8%) undergoing simultaneous cataract surgery. No surgical complications occurred during or after surgery in any case. In all cases, retinal folds within a 3-mm-diameter circle centered on the macula were present preoperatively but disappeared by 6 months postoperatively, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. We examined the relationship between the mean percentage of aniseikonia 6 months postoperatively and the preoperative MDRF. The correlation between the mean percentage of aniseikonia at 6 months postoperatively and the preoperative MDRF was also significant (y\u0026thinsp;=\u0026thinsp;0.0368x \u0026minus;\u0026thinsp;0.5893; r\u0026thinsp;=\u0026thinsp;0.467; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). According to regression line equations, the preoperative and postoperative MDRF values corresponding to the threshold at which aniseikonia interfered with daily life (aniseikonia of 3%) were 73.75 \u0026micro;m and 97.53 \u0026micro;m, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eRelationship Between Preoperative MDRF and Preoperative OCT Parameters\u003c/h2\u003e \u003cp\u003eThe correlation between preoperative MDRF and OCT parameters associated with aniseikonia, such as the mean INL and OPL-ONL thickness, CRT, and intraocular FAZ ratio, was examined. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, the preoperative MDRF was significantly correlated with the mean preoperative INL thickness (r\u0026thinsp;=\u0026thinsp;0.562, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), preoperative CRT (r\u0026thinsp;=\u0026thinsp;0.588, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and preoperative FAZ ratio (r = -0.328, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), but not with the mean preoperative OPL-ONL thickness (r\u0026thinsp;=\u0026thinsp;0.214, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.055).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eRelationship Between Preoperative Aniseikonia and Preoperative OCT Parameters\u003c/h2\u003e \u003cp\u003eWe examined the relationship between the mean percentage of aniseikonia preoperatively and preoperative OCT parameters, such as the mean INL and OPL-ONL thickness, CRT, and intraocular FAZ ratio. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the mean percentage of aniseikonia preoperatively significantly correlated with the mean preoperative INL and OPL-ONL thicknesses (r\u0026thinsp;=\u0026thinsp;0.524, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; r\u0026thinsp;=\u0026thinsp;0.259, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020; respectively) and preoperative CRT (r\u0026thinsp;=\u0026thinsp;0.331, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), but not with the preoperative FAZ ratio (r = -0.328, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.066).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMultiple Regression Analysis for Aniseikonia\u003c/h2\u003e \u003cp\u003eMultiple regression analysis was conducted with the mean percentage of aniseikonia preoperatively as the dependent variable and preoperative MDRF, mean preoperative INL and OPL-ONL thicknesses, and preoperative CRT as independent variables. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the preoperative MDRF, mean preoperative INL, and OPL-ONL thicknesses were significantly associated with the mean percentage of aniseikonia preoperatively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029, 0.006 and 0.006, respectively).\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\u003eMultiple Regression Analysis of Preoperative Aniseikonia.\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative MDRF (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative INL thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative OPL-ONL\u003c/p\u003e \u003cp\u003ethickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral retinal thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.316\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eΒ, standard regression coefficient. INL, inner nuclear layer. MDRF, maximum depth of retinal folds. OPL-ONL, outer plexiform layer-outer nuclear layer. SE, standard error.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eR\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.344.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eEffect of Surgical Removal of ERM and ILM on Visual Functions and En Face Image Findings\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, significant improvements were noted in the best-corrected visual acuity (BCVA), mean INL thickness, and CRT 6 months postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, 0.005, and \u0026lt;\u0026thinsp;0.001, respectively). However, there was no significant improvement in the mean percentage of aniseikonia (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.512). A significant increase in the mean OPL-ONL thickness was observed (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\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\u003eComparison of Preoperative and 6-Month Postoperative Visual Functions and Optical Coherence Tomography Findings.\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=\"char\" char=\"\u0026plusmn;\" 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=\"char\" char=\".\" 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\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 months postoperatively\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMRDF (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e106.4\u0026thinsp;\u0026plusmn;\u0026thinsp;41.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean aniseikonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.89\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLogMAR BCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINL thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOPL-ONL thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e101.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral retinal thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e423.7\u0026thinsp;\u0026plusmn;\u0026thinsp;79.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e359.8\u0026thinsp;\u0026plusmn;\u0026thinsp;35.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFAZ ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.443\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBCVA, best-corrected visual acuity. FAZ, foveal avascular zone. INL, inner nuclear layer. LogMAR, logarithm of the minimum angle of resolution. MDRF, maximum depth of retinal folds. OPL-ONL, outer plexiform layer-outer nuclear layer.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur current study revealed, for the first time, that both preoperative and postoperative aniseikonia caused by ERM correlate with preoperative MDRF. These results suggest that MDRF measurements may have clinical applications in determining the timing of surgery. While ERM causes aniseikonia due to retinal traction, mild aniseikonia does not adversely affect daily life. However, aniseikonia causes binocular vision dysfunction in patients with aniseikonia of \u0026ge;\u0026thinsp;3% and fusion disorder in patients with aniseikonia of \u0026ge;\u0026thinsp;5% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, preventing aniseikonia from reaching 3% is crucial in ERM treatment. Using 3% of aniseikonia as the cutoff, the MDRF value corresponding to 3% was calculated to be 73.7 \u0026micro;m based on the relationship between preoperative MDRF and preoperative aniseikonia (y\u0026thinsp;=\u0026thinsp;0.047x \u0026minus;\u0026thinsp;0.0757). Similarly, the MDRF value corresponding to 3% was calculated from the relationship between preoperative MDRF and postoperative aniseikonia (y\u0026thinsp;=\u0026thinsp;0.0329x\u0026thinsp;+\u0026thinsp;0.0159) to be 90.7 \u0026micro;m. In other words, the timing of surgical intervention to remove traction when the MDRF is between 73.7 \u0026micro;m and 90.7 \u0026micro;m can be considered before the aniseikonia significantly affects the patient's daily life. Preoperative and postoperative MDRF in ERM have also been reported to correlate with metamorphopsia [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Kanzaki et al. suggested that surgical treatment should be performed when the MDRF is between 69 \u0026micro;m and 118 \u0026micro;m, using 0.5 as the cutoff for the M-score value at which metamorphopsia affects daily life [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This indicates that the timing of surgical treatment before visual dysfunction due to aniseikonia and metamorphopsia caused by ERM interferes with daily life based on MDRF values, the timing of surgical treatment is considered to have the same level of traction for the prevention of visual function due to inequality and prevention of visual function due to metamorphopsia. The results of this study and the Kanzaki et al. study indicate that even in situations where aniseikonia and M-score cannot be measured in symptomatic patients, measurement of MDRF by OCT imaging can now tell whether a degree of traction has occurred that would require surgery.\u003c/p\u003e \u003cp\u003eAdditionally to preoperative MDRF, preoperative INL and OPL-ONL thicknesses were significant factors in the multivariate analysis for preoperative aniseikonia. Okamoto et al. reported that INL thickness was a significant factor for aniseikonia due to ERM, whereas OPL-ONL thickness was not a significant factor [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In the present study, the mean aniseikonia, mean INL thickness, and mean OPL-ONL thickness in all patients were 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8%, 49\u0026thinsp;\u0026plusmn;\u0026thinsp;13 \u0026micro;m, and 100\u0026thinsp;\u0026plusmn;\u0026thinsp;17 \u0026micro;m, respectively, compared to 6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5%, 104\u0026thinsp;\u0026plusmn;\u0026thinsp;33 \u0026micro;m, and 196\u0026thinsp;\u0026plusmn;\u0026thinsp;24 \u0026micro;m, respectively, in Okamoto et al.'s study. The difference may be because the study by Okamoto et al. was limited to ERM cases that had undergone surgery, whereas the present study included mild cases for which surgery was not indicated. Thus, in addition to MDRF and INL thicknesses, OPL-ONL thickness may also influence aniseikonia in patients with mild ERM.\u003c/p\u003e \u003cp\u003eThis study also revealed a relationship between MDRF and OCT parameters, which have previously been reported to be correlated with aniseikonia caused by ERM. Preoperative MDRF significantly correlated with preoperative INL thickness, preoperative CRT, and preoperative FAZ ratio, but not with preoperative OPL-ONL thickness. Kanzaki et al. also reported that although INL and OPL-ONL thicknesses correlated with MDRF, OPL-ONL thickness did not correlate with the amount of MDRF progression or thickness change over time [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This study revealed that an increase in INL thickness but also CRT and FAZ ratios are secondary structural changes correlating with retinal traction. Furthermore, it appears that OPL-ONL thickness has a weaker relationship with retinal traction compared to other OCT parameters. A more detailed study of the effects of retinal traction on the retinal structure is necessary.\u003c/p\u003e \u003cp\u003eIn this study, retinal folds were observed in all 29 eyes that had undergone ERM removal surgery preoperatively but had disappeared in all cases 6 months postoperatively. Retinal folds occur due to tangential traction applied to the retina [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, their disappearance indicates that the traction applied to the retina was released. However, no significant improvement in aniseikonia was observed postoperatively despite traction removal. Regarding whether aniseikonia improves with surgical intervention in patients with ERM, although there are some reports of significant improvement [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], others report no improvement [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. ERM may cause aniseikonia by altering the distribution of M\u0026uuml;ller cells and photoreceptor cells due to traction, with no postoperative improvement attributed to the unchanged cell distribution [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. This appears consistent even in cases where the traction was completely removed by surgical intervention, and all retinal folds disappeared, as in the present surgical cases. Detailed studies are needed to examine the effects of ERM traction and the surgical removal of the traction on aniseikonia.\u003c/p\u003e \u003cp\u003eThe limitations of this study include its retrospective design, small sample size, and relatively short follow-up period. Additionally, factors other than MDRF, such as retinal fold parameters (i.e., number, distribution pattern, and duration of folds), ERM components, and age-related retinal characteristics, may contribute to visual impairment in ERM. Therefore, further investigations are warranted.\u003c/p\u003e \u003cp\u003eIn conclusion, retinal traction quantified by MDRF correlates with aniseikonia, and surgery to remove retinal traction at MDRF values between 73.7 \u0026micro;m and 90.7 \u0026micro;m may prevent QOV reduction due to aniseikonia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Ethical Considerations\u003c/h2\u003e \u003cp\u003eThis was a retrospective, consecutive observational study. All investigative procedures adhered to the principles outlined in the tenets of the Declaration of Helsinki. The study was approved by the Ethics Committee of the Himeji Red Cross Hospital, Hyogo, Japan (approval no: 2022-23). Informed consent was obtained using an opt-out procedure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed the charts of a consecutive series of 81 eyes of 81 patients with unilateral idiopathic ERM who visited the Himeji Red Cross Hospital between February 1, 2019 and January 31, 2023. Patients with a history of other retinal diseases, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, uveitis, and anisometropia\u0026thinsp;\u0026gt;\u0026thinsp;1 dpt, as well as those who had undergone vitreoretinal surgery, were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOphthalmic Examinations\u003c/h2\u003e \u003cp\u003eAll patients underwent comprehensive ophthalmologic examinations before and 6 months after surgery, including BCVA testing with refraction using a 5-m Landolt C acuity chart, indirect and contact lens slit-lamp biomicroscopy, and SS-OCT (DRI OCT-1 Triton; Topcon Corporation, Tokyo, Japan).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eQuantification of aniseikonia\u003c/h2\u003e \u003cp\u003eThe New Aniseikonia Test (NAT; Handaya, Tokyo, Japan) was utilized to quantify the severity of aniseikonia. This test consists of a book and spectacles and measures aniseikonia by separating binocular vision with red and green filters. Each eye perceives a half-moon printed on a book page. Two half-moons of different sizes in each pair were arranged in series, with the difference varying in increments of 1%. The subjects wore red-green spectacles and viewed the plates to allow the right eye to see one of the half-moons in each pair and the left eye to see the other half-moon. The participants indicated the pair in which the two half-moons appeared to be of equal size. The actual size difference between the half-moons in the pair represented the percentage of the subject's aniseikonia. The NAT target size was 4 cm (visual field angle, 5.7\u0026deg;), and measurements ranging from 1\u0026ndash;24% were possible. Measurements were done at approximately 40 cm along both the vertical and horizontal meridians, and their mean values were used for data analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSS-OCT and En Face Imaging\u003c/h2\u003e \u003cp\u003eSS-OCT images were captured in both B-scan and 3D modes (3 \u0026times; 3-mm area consisting of 320 \u0026times; 320 A-scans and 6 \u0026times; 6-mm area consisting of 512 \u0026times; 512 A-scans); image analysis software, IMAGEnet6, Version 1.22 (Topcon Corporation, Tokyo, Japan), was used for en face and OCT angiography (OCTA) image construction. Based on the retinal layer boundary information, IMAGEnet6 aligned the 3D-OCT volume scan data along a specific retinal layer boundary, generating en face and OCTA images at an arbitrary depth. Additionally, CRT measurements were obtained at the fovea within a 1-mm-diameter circle using the built-in calculation system of the SS-OCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of MDRF\u003c/h2\u003e \u003cp\u003eMDRF was measured within a 3-mm-diameter circle centered at the fovea as previously described [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The 3D OCT volume scan data were flattened at the level of the ILM to visualize the black lines corresponding to the retinal folds due to retinal traction by ERM on the en face image below the ILM level. We then measured the slab depth of the en face image, in which the black lines corresponding to the deepest retinal folds disappeared within the parafoveal area (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of the FAZ Area and the Interocular Ratios of the FAZ Area\u003c/h2\u003e \u003cp\u003eSuperficial capillary plexus (SCP) en face images from 3 \u0026times; 3-mm OCTA images were used to measure the FAZ area in both eyes with the ERM and fellow eyes. The en face images of the SCP were constructed from the data 2.6 \u0026micro;m below the ILM and 15.6 \u0026micro;m below the inner plexiform layer. FAZ contour in the SCP was manually traced, and IMAGEnet6 automatically computed the surface area within the drawing-in contour. The interocular ratio of the FAZ area in the ERM eyes to that in the fellow eyes was calculated (Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of the Mean INL and ONL-OPL Thicknesses\u003c/h2\u003e \u003cp\u003eB-scan OCT images of the vertical and horizontal cross-sections through the fovea were used to measure mean INL and ONL-OPL thicknesses. Measurements were obtained from points located 500 \u0026micro;m and 1000 \u0026micro;m away from the fovea in the superior, inferior, nasal, and temporal regions (1 point at 500 \u0026micro;m and 1 at 1000 \u0026micro;m in each of the four regions; total 8 points; Supplementary Fig. \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). The average of the eight values was used for statistical analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Procedure\u003c/h2\u003e \u003cp\u003eIndications for ERM surgery included decreased visual acuity (\u0026lt;\u0026thinsp;20/20) or complaints of metamorphopsia or aniseikonia. All patients provided written informed consent preoperatively after the risks and benefits of all surgical procedures were explained to them. In all eyes, triamcinolone acetonide was used intraoperatively to facilitate the visualization of the vitreous and posterior hyaloid. After core vitrectomy using a 27-gauge microincision vitrectomy system (Constellation; Alcon Laboratories, Inc., Fort Worth, Texas, USA), the ERM and ILM were removed using end-gripping forceps. ILM peeling was performed after staining with 0.25 mg/mL brilliant blue G solution (Coonassie BBG 250; Sigma-Aldrich, St. Louis, Missouri, USA). Cataract extraction with posterior chamber intraocular lens implantation was performed before pars plana vitrectomy in all cataract cases. All the surgeries were performed by a single surgeon (M. H.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll data ware expressed the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. BCVAs were recorded as decimal values and converted to the logarithm of the minimum angle of resolution (logMAR) units for statistical analysis. Visual acuity results were presented as logMAR units and Snellen visual acuities. Statistical analyses were conducted using SPSS, version \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e24.0.0.0\u003c/span\u003e (IBM Corporation, Armonk, New York, USA). Spearman rank correlation tests were used to assess relationships between the mean percentage of aniseikonia and MDRF, mean INL and ONL-OPL thicknesses, CRT, and FAZ ratio. The relationships between MDRF and the mean INL and ONL-OPL thicknesses, CRT, and FAZ ratio were also analyzed using Spearman rank correlation tests. The mean aniseikonia, mean INL and ONL-OPL thicknesses, and CRT and FAZ ratios before and 6 months after surgery were compared using the Wilcoxon signed-rank test. A \u003cem\u003eP\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eData supporting the findings of this study are available from the corresponding author, M.H., upon reasonable request.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAdditional information\u003c/h2\u003e \u003cp\u003eThe authors report no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.H. designed and conducted the study. M.H., S.M., Y.I., and N.Y. collected the data. M.H. managed, analyzed, and interpreted the data and wrote the article. M.H., S.M., Y.I., and N.Y. critically revised the article and gave its final approval.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData supporting the findings of this study are available from the corresponding author, M.H., upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSidd, R. J., Fine, S. L., Owens, S. L. \u0026amp; Patz, A. Idiopathic preretinal gliosis. Am. J. Ophthalmol. 94, 44\u0026ndash;48 (1982).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePearlstone, A. D. The incidence of idiopathic preretinal macular gliosis. Ann. Ophthalmol. 17, 378\u0026ndash;380 (1985).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBu, S.-C., Kuijer, R., Li, X.-R., Hooymans, J. M. M. \u0026amp; Los, L. I. Idiopathic epiretinal membrane. Retina. 34, 2317\u0026ndash;2335 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinoshita, T. \u003cem\u003eet al.\u003c/em\u003e Time course of changes in metamorphopsia, visual acuity, and OCT parameters after successful epiretinal membrane surgery. Invest. Opthalmol. Vis. Sci. 53, 3592 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArimura, E. \u003cem\u003eet al.\u003c/em\u003e Correlations between M-CHARTS and PHP findings and subjective perception of metamorphopsia in patients with macular diseases. Invest. Opthalmol. Vis. Sci. 52, 128 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamoto, F., Okamoto, Y., Hiraoka, T. \u0026amp; Oshika, T. Effect of vitrectomy for epiretinal membrane on visual function and vision-related quality of life. Am. J. Ophthalmol. 147, 869\u0026ndash;874.e1 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamoto, F., Sugiura, Y., Okamoto, Y., Hiraoka, T. \u0026amp; Oshika, T. Time course of changes in aniseikonia and foveal microstructure after vitrectomy for epiretinal membrane. Ophthalmology. 121, 2255\u0026ndash;2260 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamoto, F., Sugiura, Y., Okamoto, Y., Hiraoka, T. \u0026amp; Oshika, T. Associations between metamorphopsia and foveal microstructure in patients with epiretinal membrane. Invest. Opthalmol. Vis. Sci. 53, 6770 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamoto, F., Sugiura, Y., Okamoto, Y., Hiraoka, T. \u0026amp; Oshika, T. Inner nuclear layer thickness as a prognostic factor for metamorphopsia after epiretinal membrane surgery. Retina. 35, 2107\u0026ndash;2114 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchikawa, Y., Imamura, Y. \u0026amp; Ishida, M. Associations of aniseikonia with metamorphopsia and retinal displacements after epiretinal membrane surgery. Eye. 32, 400\u0026ndash;405 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe, A., Arimoto, S. \u0026amp; Nishi, O. Correlation between metamorphopsia and epiretinal membrane optical coherence tomography findings. Ophthalmology. 116, 1788\u0026ndash;1793 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Wit, G. C. \u0026amp; Muraki, C. S. Field-dependent aniseikonia associated with an epiretinal membrane a case study. Ophthalmology. 113, 58\u0026ndash;62 (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsumi, O., Tanino, T. \u0026amp; Hirose, T. Effect of aniseikonia on binocular function. Invest. Ophthalmol. Vis. Sci. 27, 601\u0026ndash;604 (1986).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyazaki, Y. Wrinkle/slack model and finite element dynamics of membrane. Int. J. Numer. Meth. Engng. 66, 1179\u0026ndash;1209 (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoddeman, D., Drukker, J., Oomens, C. \u0026amp; Janssen, J. The wrinkling of thin membranes: part Ⅰ-theory. J. Appl. Mech. 54, 884\u0026ndash;887 (1987).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoddeman, D., Drukker, J., Oomens, C. \u0026amp; Janssen, J. The wrinkling of thin membranes: part Ⅱ-numerical analysis. J. Appl. Mech. 54, 888\u0026ndash;892 (1987).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirano, M. \u003cem\u003eet al.\u003c/em\u003e Assessment of lamellar macular hole and macular pseudohole with a combination of en face and radial B-scan optical coherence tomography imaging. Am. J. Ophthalmol. 188, 29\u0026ndash;40 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirano, M. \u003cem\u003eet al.\u003c/em\u003e En face image\u0026ndash;based analysis of retinal traction caused by epiretinal membrane and its relationship with visual functions. Retina. 40, 1262\u0026ndash;1271 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanzaki, Y. \u003cem\u003eet al.\u003c/em\u003e Objective and quantitative estimation of the optimal timing for epiretinal membrane surgery on the basis of metamorphopsia. Retina. 42, 704\u0026ndash;711 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanzaki, Y. \u003cem\u003eet al.\u003c/em\u003e Epiretinal membrane impairs the inner retinal layer in a traction force-dependent manner. Ophthalmol. Sci. 3, 100312 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatoba, R. \u003cem\u003eet al.\u003c/em\u003e Assessment of epiretinal membrane formation using en face optical coherence tomography after rhegmatogenous retinal detachment repair. Graefes Arch. Clin. Exp. Ophthalmol. 259, 2503\u0026ndash;2512 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMino, M. \u003cem\u003eet al.\u003c/em\u003e Quantitative analyses of retinal traction force and metamorphopsia in lamellar macular hole and related diseases. Ophthalmol. Sci. 3, 100305 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirata, A. \u003cem\u003eet al.\u003c/em\u003e Relationship between the morphology of the foveal avascular zone and the degree of aniseikonia before and after vitrectomy in patients with unilateral epiretinal membrane. Graefes Arch. Clin. Exp. Ophthalmol. 257, 507\u0026ndash;515 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChung, H. \u003cem\u003eet al.\u003c/em\u003e Relationship between vertical and horizontal aniseikonia scores and vertical and horizontal OCT images in idiopathic epiretinal membrane. Invest. Ophthalmol. Vis. Sci. 56, 6542\u0026ndash;6548 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen, H. \u003cem\u003eet al.\u003c/em\u003e Macular microvasculature features before and after vitrectomy in idiopathic macular epiretinal membrane: an OCT angiography analysis. Eye. 33, 619\u0026ndash;628 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitagawa, Y., Shimada, H., Shinojima, A. \u0026amp; Nakashizuka, H. Foveal avascular zone area analysis using optical coherence tomography angiography before and after idiopathic epiretinal membrane surgery. Retina. 39, 339\u0026ndash;346 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan, J., Han, S.-H., Kim, J. H. \u0026amp; Koh, H. J. Restoration of retinally induced aniseikonia in patients with epiretinal membrane after early vitrectomy. Retina. 36, 311\u0026ndash;320 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMidena, E. \u0026amp; Vujosevic, S. Metamorphopsia: an overlooked visual symptom. Ophthalmic. Res. 55, 26\u0026ndash;36 (2015).\u003c/span\u003e\u003c/li\u003e\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"aniseikonia, retina, optical coherence tomography, epiretinal membrane, retinal traction","lastPublishedDoi":"10.21203/rs.3.rs-4439805/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4439805/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe investigated the effect of retinal traction caused by epiretinal membranes (ERMs) on aniseikonia and retinal microstructures in 81 unilateral ERMs. Retinal traction was quantified by measuring the maximum depth of the retinal fold (MDRF) using en face optical coherence tomography (OCT) images. Measurements included the mean inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), central retinal thickness (CRT), and interocular ratios of the foveal avascular zone (FAZ) area (FAZ ratio). Significant correlations were found between the preoperative MDRF and preoperative aniseikonia (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), INL thickness (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), CRT (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and FAZ ratio (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). Preoperative aniseikonia was significantly correlated with preoperative INL and OPL-ONL thicknesses (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020, respectively) and CRT (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). Multiple regression analysis revealed that preoperative aniseikonia was significantly associated with preoperative MDRF, INL, and OPL-ONL thicknesses (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029, 0.006, and 0.006, respectively). Twenty-nine eyes underwent membrane peeling, resolving all retinal folds 6 months postoperatively. A significant correlation was observed between preoperative MDRF and postoperative aniseikonia (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011). Our findings suggest that retinal traction by ERM is significantly associated with aniseikonia both pre- and postoperatively, alongside other OCT parameters.\u003c/p\u003e","manuscriptTitle":"Impact of Retinal Traction Induced by Epiretinal Membrane on Aniseikonia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-06 18:45:33","doi":"10.21203/rs.3.rs-4439805/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-22T09:00:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-21T12:21:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-17T10:40:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134215090964808604569491639567543055101","date":"2024-07-16T13:25:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67789429890001226652435732670030484898","date":"2024-07-15T14:11:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-15T13:57:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-15T13:52:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-22T05:40:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-22T05:38:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-05-18T06:52:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"384a851a-aa7a-4906-87ad-83e5e9426d4a","owner":[],"postedDate":"June 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":32699908,"name":"Health sciences/Medical research"},{"id":32699909,"name":"Physical sciences/Optics and photonics"}],"tags":[],"updatedAt":"2024-10-28T16:06:12+00:00","versionOfRecord":{"articleIdentity":"rs-4439805","link":"https://doi.org/10.1038/s41598-024-72048-0","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-10-23 15:58:15","publishedOnDateReadable":"October 23rd, 2024"},"versionCreatedAt":"2024-06-06 18:45:33","video":"","vorDoi":"10.1038/s41598-024-72048-0","vorDoiUrl":"https://doi.org/10.1038/s41598-024-72048-0","workflowStages":[]},"version":"v1","identity":"rs-4439805","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4439805","identity":"rs-4439805","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}