Surgical outcomes of interventions for treating intraocular lens-induced secondary pigment dispersion syndrome: a retrospective study

Surgical outcomes of interventions for treating intraocular lens-induced secondary pigment dispersion syndrome: a retrospective study | 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 Surgical outcomes of interventions for treating intraocular lens-induced secondary pigment dispersion syndrome: a retrospective study Shuu Morita, Tatsuya Fujii, Yoshihito Sakanishi, Ayumi Usui-Ouchi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6290360/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Oct, 2025 Read the published version in International Ophthalmology → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose : Intraocular lens (IOL)-induced pigment dispersion syndrome (PDS) represents a significant clinical challenge. However, literature on treatment strategies based on intraocular pressure (IOP) is limited. In this retrospective comparative analysis, we analyzed patients with IOL-induced PDS who underwent surgical treatment, focusing on clinical outcomes and preoperative IOP. Methods : Japanese patients with glaucoma who underwent surgery for IOL-related PDS were divided into the IOL removal with scleral fixation of IOL (SFIOL) and glaucoma surgery groups. The SFIOL group was subdivided into the high- and low- pressure groups based on preoperative IOP. The main outcomes included mean IOP and cumulative success rates assessed using Kaplan–Meier curves. Results : We analyzed 24 eyes (24 patients) in the SFIOL group and 15 (15 patients) in the glaucoma surgery group. In the SFIOL low-pressure group (preoperative IOP ≤24 mmHg), normal IOP was maintained, resulting in a postoperative 1-year cumulative 100% success rate; in the high-pressure group (preoperative IOP >24 mmHg), IOP was challenging to maintain even after IOL status improvement, resulting in a 24.2% success rate. In the glaucoma surgery group (median preoperative IOP 29 mmHg), the success criterion rate for 6 ≤ IOP ≤ 21 mmHg was 100%, and 49.2% for 6 ≤ IOP ≤ 14 mmHg. Conclusion : When preoperative IOP was maintained, normal pressure could be achieved by IOL status improvement. Additional glaucoma surgery was frequently required when preoperative IOP exceeded 24 mmHg. IOL and iris alignment should be corrected when preoperative IOP is maintained at < 24 mmHg. Intraocular lens Pigment dispersion syndrome Intraocular pressure Scleral fixation Glaucoma surgery Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Pigment dispersion syndrome (PDS) caused by intraocular lenses (IOL) represents a significant clinical challenge, arising from friction between the IOL haptics or optics and the iris, leading to the dispersion of iris pigment [ 1 ]. This phenomenon can result in pigment accumulation within the trabecular meshwork (TM), contributing to elevated intraocular pressure (IOP) and subsequent secondary glaucoma (SG) [ 2 ]. Despite its recognition in the ophthalmic community [ 3 ], definitive diagnostic criteria for PDS remain elusive, underscoring the need for further investigation. The management of PDS necessitates a nuanced approach tailored to the individual patient's clinical status; however, a standardized treatment protocol is still lacking. Previous studies have reported that patients with SG caused by PDS often exhibit poor responsiveness to topical medication therapies [ 2 , 4 , 5 ]. Conversely, there are many reports of IOL replacement or removal resulting in IOP normalization, and there is a certain level of consensus that the first choice of treatment should be measured to eliminate friction between the IOL and iris [ 4 , 6 ]. Various surgical techniques have been explored, including IOL repositioning [ 6 , 7 ], exchanging a single-piece IOL with a three-piece IOL [ 6 , 8 ], and IOL removal with scleral fixation of IOL (SFIOL) [ 9 ]. Notably, even after alleviating friction, some patients may still require additional glaucoma surgery for adequate IOP control [ 8 ]. Early-stage PDS often presents with minimal subjective symptoms, complicating the decision-making process regarding the timing and necessity of surgical intervention. Currently, limited literature addresses treatment strategies for IOL-induced PDS based on IOP levels and patient characteristics. Therefore, this study comprehensively analyzed cases of patients with IOL-induced PDS who underwent surgical treatment, focusing on clinical outcomes, postoperative progression, and differences in preoperative IOP and demographic characteristics. Our objective was to provide insights into the optimal timing for surgical intervention, ultimately enhancing patient care and outcomes for this complex condition. Our goal was not only to contribute to the existing body of knowledge on PDS but also to establish a framework for improved management strategies. We anticipate that our findings will have significant implications for clinical practice and future rxfesearch in this area. Materials and Methods Study design and inclusion and exclusion criteria We retrospectively evaluated the medical records of Japanese patients with glaucoma who underwent surgical intervention for IOL-induced PDS at Juntendo University Urayasu Hospital, Chiba, Japan, between February 2018 and April 2023. The study was conducted according to the tenets of the Declaration of Helsinki; ethical approval was obtained from the Institutional Review Board of Juntendo University (E22-0212, E23-0357). The surgeon explained the purpose of the study to the patients, and their consent was documented in their medical records. The patients were divided into two groups: one group underwent IOL removal with SFIOL, combined with pars plana vitrectomy (PPV) to reduce friction between the IOL and iris (SFIOL group), and the other group underwent glaucoma surgery (glaucoma surgery group). The evaluation parameters were then assessed. Based on preoperative IOP levels, the SFIOL group was further subdivided into the low-pressure (≤ 24 mmHg) and high-pressure (> 24 mmHg) groups. All patients in the glaucoma surgery group received Ahmed Glaucoma Valve (AGV) implantation. The diagnostic criteria for PDS have not been definitively established; however, based on previous reports [1, 8, 10], the following criteria were used in this study: (1) abnormal IOL positioning; (2) contact between the IOL and iris; (3) pigment dispersion in the anterior chamber or anterior vitreous; and (4) Scheie's pigmentation classification [11] of grade II or higher, with clear asymmetry between the left and right eyes. The inclusion criteria were (1) a diagnosis of PDS, (2) age 20–80 years at the time of surgery, and (3) follow-up period of > 3 months after surgery. The exclusion criteria were (1) patients who did not consent to study participation; (2) eyes that had previously undergone any form of incisional or laser glaucoma surgery; and (3) for the glaucoma surgery group, patients who did not have IOL status improvement or who did not have IOL status improvement performed simultaneously. Surgical technique To remove the IOL, it was first repositioned onto the iris. The optic portion was then partially cut using an IOL cutter, and the IOL was extracted by rotating it through a 3-mm corneal incision [12]. Vitrectomy was performed via a 27G PPV, and SFIOL was achieved using flanged intrascleral IOL fixation with the double-needle technique [13]. The AGV plate was positioned on either the superior or inferior temporal side depending on the condition of the conjunctiva and patient surgical history and was secured to the scleral wall 9 mm from the limbus. The AGV tube tip was inserted into the ciliary sulcus or vitreous cavity, and the tube was covered with either a 3 × 6 mm autologous scleral graft or 4 × 6 mm flap of preserved human sclera. Outcome measures The preoperative backgrounds of the patients were assessed including age, operated eye, sex, preoperative logarithm of minimum angle (logMAR) visual acuity, preoperative visual field (VF), preoperative IOP, preoperative glaucoma medication score, history of or predisposition to glaucoma, and preoperative IOL status. The main outcome measures assessed were IOP, glaucoma medication scores, and cumulative success rate by the Kaplan–Meier method. Each item was surveyed both preoperatively and postoperatively. Postoperatively, each item was recorded on day 1, at week 1, and after 1, 3, 6, and 12 months in the SFIOL group and on day 1, at week 1, and after 1, 3, 6, 12, 18, and 24 months in the glaucoma surgery group. We also evaluated postoperative complications. The VF was evaluated using the mean deviation value obtained from the Humphrey Field Analyzer (HFA, ZEISS, Oberkochen, Germany). IOP measurements were obtained using a calibrated Goldmann applanation tonometer (Haag-Streit, Köniz, Switzerland) during office visits after administration of a topical anesthetic while the patient was in a seated position. The glaucoma medication score was calculated as follows: 1 point for single glaucoma eye drops, 2 points for combination glaucoma eye drops, and 1 point for each oral acetazolamide tablet. The success criteria for the SFIOL group were defined as “postoperative IOP from 6–21 mmHg.” For the glaucoma surgery group, success was defined as achieving a “20% or greater reduction in IOP compared to preoperative levels” along with two additional criteria: Criterion 1, postoperative IOP from 6–21 mmHg, and Criterion 2, postoperative IOP from 6–14 mmHg. In both groups, failure was determined if patients lost light perception or required additional glaucoma surgery. The study was discontinued for patients who underwent other surgeries, such as vitreous surgery or corneal transplantation. Statistical analyses Categorical variables were analyzed using Fisher's exact test or the chi-square test, whereas continuous variables were analyzed using the Mann–Whitney U test. Cumulative success rates were evaluated using the Kaplan–Meier method. The comparison of cumulative success rates between groups was conducted using the log-rank test. Additional statistical methods are detailed in the tables and figures. P values < 0.05 were considered statistically significant. All statistical analyses were performed using R version 4.1.2 software for Windows (R Foundation for Statistical Computing, Vienna, Austria). Results Subgroups of the SFIOL group The SFIOL group was further subdivided based on preoperative IOP levels. To establish the cutoff value for preoperative IOP relative to survival time based on the success criteria, a time-dependent receiver operating characteristic curve analysis was conducted. The analysis indicated that sensitivity and specificity were maximized when 24 mmHg was used as the cutoff value for preoperative IOP (Fig. 1). Consequently, the group was subdivided into the low (≤ 24 mmHg) and high (> 24 mmHg) pressure groups. Baseline characteristics The patient demographic characteristics are outlined in Table 1. This study investigated 24 eyes of 24 patients in the SFIOL group and 15 eyes of 15 patients in the glaucoma surgery group. In the SFIOL group, the median age (interquartile range [IQR]) was 55.00 [48.00, 79.00] years in the low-pressure group and 66.00 [51.00, 77.50] years in the high-pressure group, with no significant difference. The preoperative IOP (median [IQR]) was 21.00 [18.00, 22.00] mmHg in the low-pressure group and 31.00 [27.00, 33.00] mmHg in the high-pressure group; the IOP was significantly higher in the high-pressure group (p < 0.01). The medication score was 2.00 [0.00, 4.00] in the low-pressure group and 5.00 [4.00, 5.00] in the high-pressure group; this score was also significantly higher in the high-pressure group (p < 0.01). No differences were observed in other background factors. In contrast, the median age [IQR] in the glaucoma surgery group was 68.00 [58.00, 77.50] years, with a median preoperative IOP of 29.00 [24.00, 32.50] mmHg and median medication score of 5.00 [4.00, 6.00]. Other patient characteristics are summarized in Table 1. IOP/glaucoma medication score The results are presented in Table 2. In the SFIOL group, the preoperative IOP (median [IQR]) was 24.0 [20.8, 30.3] mmHg, which decreased to 16.0 [14.0, 16.0] mmHg at 12 months postoperatively. A significant reduction in IOP was observed for up to 6 months postoperatively; however, no statistically significant difference was noted beyond that period. The median eye drop score (median [IQR]) was 4.0 [2.0, 5.0] before surgery and 2.0 [0.8, 2.0] at 12 months after surgery. In the glaucoma surgery group, the preoperative IOP (median [IQR]) was 29.0 [24.0, 32.5] mmHg, which dropped to 12.5 [12.0, 15.3] mmHg at 24 months postoperatively, showing a significant decrease throughout the entire observation period. The median eye drop score (median [IQR]) was 5.0 [4.0, 6.0] preoperatively and 2.5 [0.5, 3.0] at 24 months postoperatively, although this change was not statistically significant. Cumulative success rate The Kaplan–Meier survival curve rates at 6 and 12 months postoperatively in the low-pressure group (SFIOL group) were 100% and 100%, respectively, whereas the corresponding values in the high-pressure group (SFIOL group) were 36.4% and 24.2%, respectively (Fig. 2). There was a statistically significant difference in the survival curve rates between the low- and high-pressure groups (p < 0.01). The results of the glaucoma surgery group are presented in Figures 3 and 4. For Criterion 1 (6 ≤ IOP ≤ 21 mmHg), the cumulative success rates at 6, 12, and 24 months postoperatively in the glaucoma surgery group were 100%, 100%, and 100%, respectively (Fig. 3). For Criterion 2 (6 ≤ IOP ≤ 14 mmHg), the cumulative success rates at 6, 12, and 24 months postoperatively in the glaucoma surgery group were 64.6%, 49.2%, and 49.2%, respectively (Fig. 4). Safety Table 3 lists the complications recorded during this study. No serious complications, such as suprachoroidal hemorrhage or endophthalmitis, were observed. The complications did not differ significantly between the groups. The complications classified as “Others” were reverse pupillary block in the SFIOL group and transient elevation of IOP in the glaucoma surgery group. Reverse pupillary block required additional surgery. The transient elevation of IOP was reduced to normal levels by glaucoma medications and gradually improved thereafter. Discussion In this study, we examined the postoperative outcomes of IOL-related PDS in a larger number of patients than previously reported. Additionally, we clarified the differences in outcomes based on IOP levels and evaluated the effect of AGV implantation in patients with elevated IOP that persisted despite resolving the friction between the IOL and iris. First, regarding the background of patients who developed PDS, more than 70% of those in the high-pressure SFIOL group and glaucoma surgery group had predisposing factors that were expected to cause reduced TM outflow function, such as primary open-angle glaucoma (POAG) and pseudoexfoliation syndrome. Glaucoma is more likely to become apparent when TM outflow function is weakened [8], and patients with a background of POAG or pseudoexfoliation syndrome often require glaucoma surgery [14]. In other words, patients with a history of or predisposing factors to glaucoma may have higher IOP and may be more difficult to treat if they develop IOL-related PDS. Second, we discuss the surgical technique employed. In the patients with preoperative IOP levels in the upper 20s or higher and VF damage progression within the central 10° despite the maximum tolerated dose of glaucoma medication, as well as in those who requested general anesthesia and whose maximum preoperative IOP was excessively high (>40 mmHg), we performed simultaneous IOL status improvement and AGV insertion. In other instances, AGV insertion was performed after IOL status improvement when IOP control remained inadequate despite the use of glaucoma medication. Although there are reports indicating that IOL status improvement can effectively control IOP within the normal range [6-9], some patients require glaucoma surgery [8, 15]. However, predicting the necessity for glaucoma surgery based solely on preoperative conditions is challenging. Furthermore, postoperative hypotony has been reported to be a complication associated with SFIOL [13, 16]. Consequently, in our hospital, we prioritize correcting the IOL status before proceeding with AGV insertion if IOP control is not achieved. In patients whose preoperative VF defect approaches the central 10° or preoperative IOP is significantly elevated, we determine whether simultaneous glaucoma surgery is necessary and perform the IOL status improvement and AGV insertion concurrently. Previous reports have also indicated that tube shunt surgery is preferable in cases in which optic nerve damage has already occurred [6]. Various surgical approaches can be selected for IOL-related PDS depending on the circumstances, ranging from outflow reconstruction and minimally invasive glaucoma surgery [17] to trabeculectomy [18] and tube shunt surgery [6]. At our facility, we frequently opt for IOL removal combined with PPV and SFIOL to improve the IOL status. Therefore, we select AGV as a treatment option, which provides a favorable balance of safety and efficacy even in patients with an avitreous eye and a single chamber. Third, we address the postoperative outcomes of the SFIOL group. In the low-pressure group (preoperative IOP was ≤ 24 mmHg), normal IOP was maintained (use of glaucoma medication is permitted), following IOL status improvement, resulting in a cumulative success rate of 100% at 12 months. Conversely, in the high-pressure group (preoperative IOP exceeded 24 mmHg), many patients were unable to maintain IOP within the normal range even after IOL status improvement, necessitating additional glaucoma surgery; thus, the cumulative success rate was only 24.2% at 12 months after surgery for this group. This indicates that when IOP was preoperatively maintained below 20 mmHg using glaucoma medication, normal pressure could be achieved by improving the frictional relationship between the IOL and iris. However, when preoperative IOP exceeded 24 mmHg, additional glaucoma surgery was frequently required, even after improving the frictional relationship. A report on cases of PDS/SG resulting from ciliary sulcus fixation of a single-piece IOL indicated that the incidence of patients requiring glaucoma surgery was significantly higher among those with elevated IOP [8]. TM cells are recognized for their high capacity to phagocytize pigment granules [19]. An experiment involving the injection of pigment particles into the anterior chamber of monkeys revealed only a transient decrease in aqueous humor outflow [20]. Sakuma et al. [21] reported a case of IOL-induced PDS requiring trabeculectomy following IOL removal, highlighting the pathological findings of significant pigmentation within the TM and a decrease in TM cells. However, despite these changes, no obstruction of Schlemm's canal was observed. Conversely, Gottanka et al. [22] documented the eventual fusion of trabecular beams and obstruction of Schlemm's canal. A pathological study of IOL-induced PDS indicated that while TM damage is reversible in some cases, it results in permanent loss of TM structure due to necrosis induced by pigment in others [1]. The anticipated clinical course, based on these previous findings and our results, is summarized in Table 4. Initially, the pigment appears scattered and ultimately accumulates within the TM, hindering processing and leading to irreversible changes, such as the fusion of TM beams and occlusion of Schlemm's canal. Our study also suggested that in patients with higher IOP, even with the administration of glaucoma medication, the degree of irreversible damage to the TM was greater, particularly when IOP exceeded 24 mmHg; therefore, caution should be exercised in such situations. The treatment outcomes of AGV insertion in patients with irreversible TM dysfunction (glaucoma surgery group) were favorable when the success criterion was defined as the maintenance of IOP within the normal range (≤ 21 mmHg). However, when the target IOP was set at ≤ 14 mmHg, the success rate at 12 months was only 49.2%, indicating suboptimal results. Previous reports on POAG suggest that a lower target IOP is required for managing more advanced glaucoma [23, 24]. Consequently, we contend that invasive interventions aimed at reducing IOP should be considered before optic nerve and VF damage progress to more severe stages. This study has a few limitations. These include the study design involving a retrospective comparative analysis, relatively small number of cases, inability to quantify and assess the positional relationship between the IOL and iris preoperatively, and inability to evaluate the status of the TM postoperatively (such as the degree of pigmentation). Additionally, the glaucoma surgery group included procedures performed simultaneously with IOL status improvement, which may have influenced the outcomes. In conclusion, in the cases of IOL-related PDS, friction between the malpositioned IOL and iris led to pigment dispersion, causing damage to the TM and resulting in a progressive decline in its function. As the condition progresses, the IOP gradually increases, and as management with glaucoma medication becomes inadequate to control the IOP irreversible damage eventually occurs. Our study results suggest that addressing the misalignment between the IOL and iris to eliminate friction should be considered while the IOP remains below 24 mmHg with the use of glaucoma medication. Glaucoma surgery is likely to be necessary when IOP exceeds the late 20s, even with the maximum tolerated doses of glaucoma medication. The intermediate outcomes of AGV insertion in such cases were favorable when success was defined as achieving IOP within the normal range. In future research, we aim to clarify the optimal timing for recommending IOL status improvement and the conditions under which glaucoma surgery is likely to be necessary by refining our internal treatment protocol and increasing the number of cases for evaluation. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Compliance with Ethical Standards Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Juntendo University (16/09/2022/E22-0212, 09/01/20242024.1.9/E23-0357). Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent to Publish: The authors affirm that human research participants provided informed consent for publication of the images in Figures. Data, Material and/or Code Availability: All data supporting the findings of this study are available within the paper and its Supplementary Information. Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Shuu Morita, Tatsuya Fujii. The first draft of the manuscript was written by Shuu Morita and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Van Mierlo C, Pinto LA, Stalmans I (2015) Surgical management of iatrogenic pigment dispersion glaucoma. J Curr Glaucoma Pract 9:28-32. https://doi.org/10.5005/jp-journals-10008-1180 Uy HS , Chan PST (2006) Pigment release and secondary glaucoma after implantation of single-piece acrylic intraocular lenses in the ciliary sulcus. Am J Ophthalmol 142:330-332. https://doi.org/10.1016/j.ajo.2006.02.033 Durr GM, Ahmed IIK (2021) Intraocular lens complications: decentration, uveitis-glaucoma-hyphema syndrome, opacification, and refractive surprises. Ophthalmology 128:e186-e194. https://doi.org/10.1016/j.ophtha.2020.07.004 Chang DF (2009) Repositioning technique and rate for toric intraocular lenses. 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Supplementary Files Book1.xlsx Tables.docx Cite Share Download PDF Status: Published Journal Publication published 23 Oct, 2025 Read the published version in International Ophthalmology → Version 1 posted Editorial decision: Revision requested 19 Aug, 2025 Reviews received at journal 17 Aug, 2025 Reviewers agreed at journal 30 Jul, 2025 Reviews received at journal 08 Jun, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers invited by journal 27 Mar, 2025 Editor assigned by journal 24 Mar, 2025 Submission checks completed at journal 24 Mar, 2025 First submitted to journal 23 Mar, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6290360","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":441676871,"identity":"914ac9a4-989a-42db-acdb-abe7ec0d4e3d","order_by":0,"name":"Shuu Morita","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYNACAwYGfoYDYCZjA5jiIajFgEGyAajlAPFagNYYgCxBaMED5Bu4Ex9XFPyRNz54xuzxh4o7sv0MzA8/MMjcwW38Ad7NhmcMDAy3HThjbnDgzDPjmQ1sxhIMPM9wa5F/u02ywcCAEajFTOJg2+HEDQcYzIB+OYzHYbxgLfabG0Ba/oG0sH/Dq4XhAERL4gYGkJYGkBYe/LaA/dJgYJw848CxMokzxw4bz2zmKZZIwOMXoMM2Pmz4I2fbP+PwNomKmsOy/eztGz987MEdYgggcQDKYAbixJ4DuFXCAX8DMu8HMVpGwSgYBaNghAAA2BlbOHl2l+IAAAAASUVORK5CYII=","orcid":"","institution":"Juntendo University Urayasu Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shuu","middleName":"","lastName":"Morita","suffix":""},{"id":441676872,"identity":"153af8b7-1854-4e37-afa1-e254799d1548","order_by":1,"name":"Tatsuya Fujii","email":"","orcid":"","institution":"Juntendo University Urayasu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tatsuya","middleName":"","lastName":"Fujii","suffix":""},{"id":441676873,"identity":"b9eb94a3-42b9-432c-8289-7ed5bfeb66d0","order_by":2,"name":"Yoshihito Sakanishi","email":"","orcid":"","institution":"Juntendo University Urayasu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yoshihito","middleName":"","lastName":"Sakanishi","suffix":""},{"id":441676874,"identity":"cb4c3218-022e-401f-bd77-c43bfaa82746","order_by":3,"name":"Ayumi Usui-Ouchi","email":"","orcid":"","institution":"Juntendo University Urayasu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ayumi","middleName":"","lastName":"Usui-Ouchi","suffix":""},{"id":441676875,"identity":"4610c7b4-639b-4f18-ba13-b999cbc73fbb","order_by":4,"name":"Shintaro Nakao","email":"","orcid":"","institution":"Juntendo University","correspondingAuthor":false,"prefix":"","firstName":"Shintaro","middleName":"","lastName":"Nakao","suffix":""},{"id":441676876,"identity":"88e185cd-53dc-47de-9e27-84b349dd0e8e","order_by":5,"name":"Nobuyuki Ebihara","email":"","orcid":"","institution":"Juntendo University Urayasu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nobuyuki","middleName":"","lastName":"Ebihara","suffix":""}],"badges":[],"createdAt":"2025-03-23 22:53:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6290360/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6290360/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10792-025-03799-6","type":"published","date":"2025-10-23T16:17:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80807992,"identity":"d7c6a005-583b-445f-9944-cc6fa70ece9f","added_by":"auto","created_at":"2025-04-17 09:42:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39986,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime-dependent receiver operating characteristic (ROC) curve analysis. \u003c/strong\u003eThreshold that maximizes the sum of sensitivity and specificity = 24,\u003c/p\u003e\n\u003cp\u003esensitivity = 1.00, specificity = 0.83. The cutoff value for the ROC curve of preoperative intraocular pressure against survival time was 24 mmHg, with a sensitivity of 1.00 and specificity of 0.83\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/8791af6e9ea544e8d2926d19.png"},{"id":80808493,"identity":"782b0f53-e7a2-4f2e-bd4b-779fe0f3d442","added_by":"auto","created_at":"2025-04-17 09:50:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27966,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of cumulative success rates in the SFIOL group (low-pressure group vs. high-pressure group). \u003c/strong\u003eThe cumulative success rates at 6 and 12 months postoperatively were 100% and 100%, respectively, in the low-pressure group and 36.4% and 24.2%, respectively, in the high-pressure group. Log-rank test: p＜0.01\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/efe9c1e9cacbb911bd26fca5.png"},{"id":80808492,"identity":"a7fffe3d-9c59-4bfb-b14a-e7fb041bdbfb","added_by":"auto","created_at":"2025-04-17 09:50:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44113,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative success rates evaluated based on Criterion 1: 6 ≤ IOP ≤ 21 mmHg (glaucoma surgery group). \u003c/strong\u003eThe cumulative success rates at 6, 12, and 24 months postoperatively in the glaucoma surgery group were 100%, 100%, and 100%, respectively\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/2885dec04e35f7b4b24f8532.png"},{"id":80807996,"identity":"73c2f016-27bd-4737-bb7b-5fa7fe64e3d3","added_by":"auto","created_at":"2025-04-17 09:42:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28485,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative success rates evaluated based on Criterion 2: 6 ≤ IOP ≤ 14 mmHg (glaucoma surgery group). \u003c/strong\u003eThe cumulative success rates at 6 12, and 24 months postoperatively in the glaucoma surgery group were 64.6%, 49.2%, and 49.2%, respectively\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/006dfd3337d5115611d307cd.png"},{"id":94490779,"identity":"f3d3a3a9-2be6-4a7d-ac40-4fffdc2643ab","added_by":"auto","created_at":"2025-10-27 17:15:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":835818,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/d5b88339-63b6-4fd7-8e45-34fcf812ecb7.pdf"},{"id":80807997,"identity":"df25b325-a255-438e-acbe-db9991e19412","added_by":"auto","created_at":"2025-04-17 09:42:28","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25523,"visible":true,"origin":"","legend":"","description":"","filename":"Book1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/a45b0bdd8951d0362c4629da.xlsx"},{"id":80807994,"identity":"a4ccb4a3-a404-4d33-9dd1-53fd42fae512","added_by":"auto","created_at":"2025-04-17 09:42:28","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":47512,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6290360/v1/2ff676e7f19ea61ed287e482.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surgical outcomes of interventions for treating intraocular lens-induced secondary pigment dispersion syndrome: a retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePigment dispersion syndrome (PDS) caused by intraocular lenses (IOL) represents a significant clinical challenge, arising from friction between the IOL haptics or optics and the iris, leading to the dispersion of iris pigment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This phenomenon can result in pigment accumulation within the trabecular meshwork (TM), contributing to elevated intraocular pressure (IOP) and subsequent secondary glaucoma (SG) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite its recognition in the ophthalmic community [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], definitive diagnostic criteria for PDS remain elusive, underscoring the need for further investigation.\u003c/p\u003e \u003cp\u003eThe management of PDS necessitates a nuanced approach tailored to the individual patient's clinical status; however, a standardized treatment protocol is still lacking. Previous studies have reported that patients with SG caused by PDS often exhibit poor responsiveness to topical medication therapies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Conversely, there are many reports of IOL replacement or removal resulting in IOP normalization, and there is a certain level of consensus that the first choice of treatment should be measured to eliminate friction between the IOL and iris [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Various surgical techniques have been explored, including IOL repositioning [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], exchanging a single-piece IOL with a three-piece IOL [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and IOL removal with scleral fixation of IOL (SFIOL) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Notably, even after alleviating friction, some patients may still require additional glaucoma surgery for adequate IOP control [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Early-stage PDS often presents with minimal subjective symptoms, complicating the decision-making process regarding the timing and necessity of surgical intervention.\u003c/p\u003e \u003cp\u003eCurrently, limited literature addresses treatment strategies for IOL-induced PDS based on IOP levels and patient characteristics. Therefore, this study comprehensively analyzed cases of patients with IOL-induced PDS who underwent surgical treatment, focusing on clinical outcomes, postoperative progression, and differences in preoperative IOP and demographic characteristics. Our objective was to provide insights into the optimal timing for surgical intervention, ultimately enhancing patient care and outcomes for this complex condition. Our goal was not only to contribute to the existing body of knowledge on PDS but also to establish a framework for improved management strategies. We anticipate that our findings will have significant implications for clinical practice and future rxfesearch in this area.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy design and inclusion and exclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively evaluated the medical records of Japanese patients with glaucoma who underwent surgical intervention for IOL-induced PDS at Juntendo University Urayasu Hospital, Chiba, Japan, between February 2018 and April 2023. The study was conducted according to the tenets of the Declaration of Helsinki; ethical approval was obtained from the Institutional Review Board of Juntendo University (E22-0212, E23-0357). The surgeon explained the purpose of the study to the patients, and their consent was documented in their medical records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patients were divided into two groups: one group underwent IOL removal with SFIOL, combined with pars plana vitrectomy (PPV) to reduce friction between the IOL and iris (SFIOL group), and the other group underwent glaucoma surgery (glaucoma surgery group). The evaluation parameters were then assessed. Based on preoperative IOP levels, the SFIOL group was further subdivided into the low-pressure (\u0026le; 24 mmHg) and high-pressure (\u0026gt; 24 mmHg) groups. All patients in the glaucoma surgery group received Ahmed Glaucoma Valve (AGV) implantation.\u003c/p\u003e\n\u003cp\u003eThe diagnostic criteria for PDS have not been definitively established; however, based on previous reports [1, 8, 10], the following criteria were used in this study: (1) abnormal IOL positioning; (2) contact between the IOL and iris; (3) pigment dispersion in the anterior chamber or anterior vitreous; and (4) Scheie\u0026apos;s pigmentation classification [11] of grade II or higher, with clear asymmetry between the left and right eyes.\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria were (1) a diagnosis of PDS, (2) age 20\u0026ndash;80 years at the time of surgery, and (3) follow-up period of \u0026gt; 3 months after surgery. The exclusion criteria were (1) patients who did not consent to study participation; (2) eyes that had previously undergone any form of incisional or laser glaucoma surgery; and (3) for the glaucoma surgery group, patients who did not have IOL status improvement or who did not have IOL status improvement performed simultaneously.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSurgical technique\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo remove the IOL, it was first repositioned onto the iris. The optic portion was then partially cut using an IOL cutter, and the IOL was extracted by rotating it through a 3-mm corneal incision [12]. Vitrectomy was performed via a 27G PPV, and SFIOL was achieved using flanged intrascleral IOL fixation with the double-needle technique [13]. The AGV plate was positioned on either the superior or inferior temporal side depending on the condition of the conjunctiva and patient surgical history and was secured to the scleral wall 9 mm from the limbus. The AGV tube tip was inserted into the ciliary sulcus or vitreous cavity, and the tube was covered with either a 3 \u0026times; 6 mm autologous scleral graft or 4 \u0026times; 6 mm flap of preserved human sclera.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOutcome measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe preoperative backgrounds of the patients were assessed including age, operated eye, sex, preoperative logarithm of minimum angle (logMAR) visual acuity, preoperative visual field (VF), preoperative IOP, preoperative glaucoma medication score, history of or predisposition to glaucoma, and preoperative IOL status.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main outcome measures assessed were IOP, glaucoma medication scores, and cumulative success rate by the Kaplan\u0026ndash;Meier method. Each item was surveyed both preoperatively and postoperatively.\u0026nbsp;Postoperatively, each item was recorded on day 1, at week 1, and after 1, 3, 6, and 12 months in the SFIOL group and on day 1, at week 1, and after 1, 3, 6, 12, 18, and 24 months in the glaucoma surgery group. We also evaluated postoperative complications.\u003c/p\u003e\n\u003cp\u003eThe VF was evaluated using the mean deviation value obtained from the Humphrey Field Analyzer (HFA, ZEISS, Oberkochen, Germany). IOP measurements were obtained using a calibrated Goldmann applanation tonometer (Haag-Streit, K\u0026ouml;niz, Switzerland) during office visits after administration of a topical anesthetic while the patient was in a seated position. The glaucoma medication score was calculated as follows: 1 point for single glaucoma eye drops, 2 points for combination glaucoma eye drops, and 1 point for each oral acetazolamide tablet.\u003c/p\u003e\n\u003cp\u003eThe success criteria for the SFIOL group were defined as \u0026ldquo;postoperative IOP from 6\u0026ndash;21 mmHg.\u0026rdquo; For the glaucoma surgery group, success was defined as achieving a \u0026ldquo;20% or greater reduction in IOP compared to preoperative levels\u0026rdquo; along with two additional criteria: Criterion 1, postoperative IOP from 6\u0026ndash;21 mmHg, and Criterion 2, postoperative IOP from 6\u0026ndash;14 mmHg. In both groups, failure was determined if patients lost light perception or required additional glaucoma surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was discontinued for patients who underwent other surgeries, such as vitreous surgery or corneal transplantation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analyses\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCategorical variables were analyzed using Fisher\u0026apos;s exact test or the chi-square test, whereas continuous variables were analyzed using the Mann\u0026ndash;Whitney U test. Cumulative success rates were evaluated using the Kaplan\u0026ndash;Meier method.\u0026nbsp;The comparison of cumulative success rates between groups was conducted using the log-rank test. Additional statistical methods are detailed in the tables and figures. P\u003cem\u003e\u0026nbsp;\u003c/em\u003evalues \u003cem\u003e\u0026lt;\u0026nbsp;\u003c/em\u003e0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using R version 4.1.2 software for Windows (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSubgroups of the SFIOL group\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SFIOL group was further subdivided based on preoperative IOP levels. To establish the cutoff value for preoperative IOP relative to survival time based on the success criteria, a time-dependent receiver operating characteristic curve analysis was conducted. The analysis indicated that sensitivity and specificity were maximized when 24 mmHg was used as the cutoff value for preoperative IOP (Fig. 1). Consequently, the group was subdivided into the low (\u0026le; 24 mmHg) and high (\u0026gt; 24 mmHg) pressure groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBaseline characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient demographic characteristics are outlined in Table 1. This study investigated 24 eyes of 24 patients in the SFIOL group and 15 eyes of 15 patients in the glaucoma surgery group. In the SFIOL group, the median age (interquartile range [IQR]) was 55.00 [48.00, 79.00] years in the low-pressure group and 66.00 [51.00, 77.50] years in the high-pressure group, with no significant difference. The preoperative IOP (median [IQR]) was 21.00 [18.00, 22.00] mmHg in the low-pressure group and 31.00 [27.00, 33.00] mmHg in the high-pressure group; the IOP was significantly higher in the high-pressure group (p \u0026lt; 0.01). The medication score was 2.00 [0.00, 4.00] in the low-pressure group and 5.00 [4.00, 5.00] in the high-pressure group; this score was also significantly higher in the high-pressure group (p \u0026lt; 0.01). No differences were observed in other background factors. In contrast, the median age [IQR] in the glaucoma surgery group was 68.00 [58.00, 77.50] years, with a median preoperative IOP of 29.00 [24.00, 32.50] mmHg and median medication score of 5.00 [4.00, 6.00]. Other patient characteristics are summarized in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIOP/glaucoma medication score\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results are presented in Table 2. In the SFIOL group, the preoperative IOP (median [IQR]) was 24.0 [20.8, 30.3] mmHg, which decreased to 16.0 [14.0, 16.0] mmHg at 12 months postoperatively. A significant reduction in IOP was observed for up to 6 months postoperatively; however, no statistically significant difference was noted beyond that period. The median eye drop score (median [IQR]) was 4.0 [2.0, 5.0] before surgery and 2.0 [0.8, 2.0] at 12 months after surgery. In the glaucoma surgery group, the preoperative IOP (median [IQR]) was 29.0 [24.0, 32.5] mmHg, which dropped to 12.5 [12.0, 15.3] mmHg at 24 months postoperatively, showing a significant decrease throughout the entire observation period. The median eye drop score (median [IQR]) was 5.0 [4.0, 6.0] preoperatively and 2.5 [0.5, 3.0] at 24 months postoperatively, although this change was not statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCumulative success rate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Kaplan\u0026ndash;Meier survival curve rates at 6 and 12 months postoperatively in the low-pressure group (SFIOL group) were 100% and 100%, respectively, whereas the corresponding values in the high-pressure group (SFIOL group) were 36.4% and 24.2%, respectively (Fig. 2). There was a statistically significant difference in the survival curve rates between the low- and high-pressure groups (p\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u0026lt; 0.01).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results of the glaucoma surgery group are presented in Figures 3 and 4. For Criterion 1 (6 \u0026le; IOP \u0026le; 21 mmHg), the cumulative success rates at 6, 12, and 24 months postoperatively in the glaucoma surgery group were 100%, 100%, and 100%, respectively (Fig. 3). For Criterion 2 (6 \u0026le; IOP \u0026le; 14 mmHg), the cumulative success rates at 6, 12, and 24 months postoperatively in the glaucoma surgery group were 64.6%, 49.2%, and 49.2%, respectively (Fig. 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSafety\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 lists the complications recorded during this study. No serious complications, such as suprachoroidal hemorrhage or endophthalmitis, were observed. The complications did not differ significantly between the groups. The complications classified as \u0026ldquo;Others\u0026rdquo; were reverse pupillary block in the SFIOL group and transient elevation of IOP in the glaucoma surgery group. Reverse pupillary block required additional surgery. The transient elevation of IOP was reduced to normal levels by glaucoma medications and gradually improved thereafter.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we examined the postoperative outcomes of IOL-related PDS\u0026nbsp;in a larger number of patients than previously reported. Additionally, we clarified the differences in outcomes based on IOP levels and evaluated the effect of AGV implantation in patients with elevated IOP that persisted despite resolving the friction between the IOL and iris.\u003c/p\u003e\n\u003cp\u003eFirst, regarding the background of patients who developed PDS, more than 70% of those in the high-pressure SFIOL group and glaucoma surgery group had predisposing factors that were expected to cause reduced TM outflow function, such as primary open-angle glaucoma (POAG) and pseudoexfoliation syndrome. Glaucoma is more likely to become apparent when TM outflow function is weakened [8], and patients with a background of POAG or pseudoexfoliation syndrome often require glaucoma surgery [14]. In other words, patients with a history of or predisposing factors to glaucoma may have higher IOP and may be more difficult to treat if they develop IOL-related PDS.\u003c/p\u003e\n\u003cp\u003eSecond, we discuss the surgical technique employed. In the patients with preoperative IOP levels in the upper 20s or higher and VF damage progression within the central 10\u0026deg; despite the maximum tolerated dose of glaucoma medication, as well as in those who requested general anesthesia and whose maximum preoperative IOP was excessively high (\u0026gt;40 mmHg), we performed simultaneous IOL status improvement and AGV insertion. In other instances, AGV insertion was performed after IOL status improvement when IOP control remained inadequate despite the use of glaucoma medication. Although there are reports indicating that IOL status improvement can effectively control IOP within the normal range [6-9], some patients require glaucoma surgery [8, 15]. However, predicting the necessity for glaucoma surgery based solely on preoperative conditions is challenging. Furthermore, postoperative hypotony has been reported to be a complication associated with SFIOL [13, 16]. Consequently, in our hospital, we prioritize correcting the IOL status before proceeding with AGV insertion if IOP control is not achieved. In patients whose preoperative VF defect approaches the central 10\u0026deg; or preoperative IOP is significantly elevated, we determine whether simultaneous glaucoma surgery is necessary and perform the IOL status improvement and AGV insertion concurrently. Previous reports have also indicated that tube shunt surgery is preferable in cases in which optic nerve damage has already occurred [6]. Various surgical approaches can be selected for IOL-related PDS depending on the circumstances, ranging from outflow reconstruction and minimally invasive glaucoma surgery [17] to trabeculectomy [18] and tube shunt surgery [6]. At our facility, we frequently opt for IOL removal combined with PPV and SFIOL to improve the IOL status. Therefore, we select AGV as a treatment option, which provides a favorable balance of safety and efficacy even in patients with an avitreous eye\u0026nbsp;and\u0026nbsp;a single chamber.\u003c/p\u003e\n\u003cp\u003eThird, we address the postoperative outcomes of the SFIOL group. In the low-pressure group (preoperative IOP was \u0026le; 24 mmHg), normal IOP was maintained (use of glaucoma medication is permitted), following IOL status improvement, resulting in a cumulative success rate of 100% at 12 months. Conversely, in the high-pressure group (preoperative IOP exceeded 24 mmHg), many patients were unable to maintain IOP within the normal range even after IOL status improvement, necessitating additional glaucoma surgery; thus, the cumulative success rate was only 24.2% at 12 months after surgery for this group. This indicates that when IOP was preoperatively maintained below 20 mmHg using glaucoma medication, normal pressure could be achieved by improving the frictional relationship between the IOL and iris. However, when preoperative IOP exceeded 24 mmHg, additional glaucoma surgery was frequently required, even after improving the frictional relationship. A report on cases of PDS/SG resulting from ciliary sulcus fixation of a single-piece IOL indicated that the incidence of patients requiring glaucoma surgery was significantly higher among those with elevated IOP [8]. TM cells are recognized for their high capacity to phagocytize pigment granules [19]. An experiment involving the injection of pigment particles into the anterior chamber of monkeys revealed only a transient decrease in aqueous humor outflow [20]. Sakuma et al. [21] reported a case of IOL-induced PDS requiring trabeculectomy following IOL removal, highlighting the pathological findings of significant pigmentation within the TM and a decrease in TM cells.\u0026nbsp;However, despite these changes, no obstruction of Schlemm\u0026apos;s canal was observed. Conversely, Gottanka et al. [22] documented the eventual fusion of trabecular beams and obstruction of Schlemm\u0026apos;s canal. A pathological study of IOL-induced PDS indicated that while TM damage is reversible in some cases, it results in permanent loss of TM structure due to necrosis induced by pigment in others [1]. The anticipated clinical course, based on these previous findings and our results, is summarized in Table 4. Initially, the pigment appears scattered and ultimately accumulates within the TM, hindering processing and leading to irreversible changes, such as the fusion of TM beams and occlusion of Schlemm\u0026apos;s canal. Our study also suggested that in patients with higher IOP, even with the administration of glaucoma medication, the degree of irreversible damage to the TM was greater, particularly when IOP exceeded 24 mmHg; therefore, caution should be exercised in such situations.\u003c/p\u003e\n\u003cp\u003eThe treatment outcomes of AGV insertion in patients with irreversible TM dysfunction (glaucoma surgery group) were favorable when the success criterion was defined as the maintenance of IOP within the normal range (\u0026le; 21 mmHg). However, when the target IOP was set at \u0026le; 14 mmHg, the success rate at 12 months was only 49.2%, indicating suboptimal results. Previous reports on POAG suggest that a lower target IOP is required for managing more advanced glaucoma [23, 24]. Consequently, we contend that invasive interventions aimed at reducing IOP should be considered before optic nerve and VF damage progress to more severe stages.\u003c/p\u003e\n\u003cp\u003eThis study has a few limitations. These include the study design involving a retrospective comparative analysis, relatively small number of cases, inability to quantify and assess the positional relationship between the IOL and iris preoperatively, and inability to evaluate the status of the TM postoperatively (such as the degree of pigmentation). Additionally, the glaucoma surgery group included procedures performed simultaneously with IOL status improvement, which may have influenced the outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, in the cases of IOL-related PDS, friction between the malpositioned IOL and iris led to pigment dispersion, causing damage to the TM and resulting in a progressive decline in its function. As the condition progresses, the IOP gradually increases, and as management with glaucoma medication becomes inadequate to control the IOP irreversible damage eventually occurs. Our study results suggest that addressing the misalignment between the IOL and iris to eliminate friction should be considered while the IOP remains below 24 mmHg with the use of glaucoma medication. Glaucoma surgery is likely to be necessary when IOP exceeds the late 20s, even with the maximum tolerated doses of glaucoma medication. The intermediate outcomes of AGV insertion in such cases were favorable when success was defined as achieving IOP within the normal range. In future research, we aim to clarify the optimal timing for recommending IOL status improvement and the conditions under which glaucoma surgery is likely to be necessary by refining our internal treatment protocol and increasing the number of cases for evaluation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e This study was performed in line with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Juntendo University (16/09/2022/E22-0212, 09/01/20242024.1.9/E23-0357).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish:\u0026nbsp;\u003c/strong\u003eThe authors affirm that human research participants provided informed consent for publication of the images in Figures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData, Material and/or Code Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its Supplementary Information.\u0026nbsp;Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Shuu Morita, Tatsuya Fujii. The first draft of the manuscript was written by Shuu Morita and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVan Mierlo C, Pinto LA, Stalmans I (2015) Surgical management of iatrogenic pigment dispersion glaucoma. J Curr Glaucoma Pract 9:28-32. https://doi.org/10.5005/jp-journals-10008-1180\u003c/li\u003e\n\u003cli\u003eUy HS\u003csup\u003e \u003c/sup\u003e, Chan PST (2006) Pigment release and secondary glaucoma after implantation of single-piece acrylic intraocular lenses in the ciliary sulcus. Am J Ophthalmol 142:330-332. https://doi.org/10.1016/j.ajo.2006.02.033\u003c/li\u003e\n\u003cli\u003eDurr GM, Ahmed IIK (2021) Intraocular lens complications: decentration, uveitis-glaucoma-hyphema syndrome, opacification, and refractive surprises. Ophthalmology 128:e186-e194. https://doi.org/10.1016/j.ophtha.2020.07.004\u003c/li\u003e\n\u003cli\u003eChang DF (2009) Repositioning technique and rate for toric intraocular lenses. J Cataract Refract Surg 35:1315-1316. https://doi.org/10.1016/j.jcrs.2009.02.035\u003c/li\u003e\n\u003cli\u003eChang SH, Wu WC, Wu SC (2013) Late-onset secondary pigmentary glaucoma following foldable intraocular lenses implantation in the ciliary sulcus: a long-term follow-up study. BMC Ophthalmol 13:22. https://doi.org/10.1186/1471-2415-13-22 \u003c/li\u003e\n\u003cli\u003eElhusseiny AM, Lee RK, Smiddy WE (2020) Surgical management of uveitis-glaucoma-hyphema syndrome. Int J Ophthalmol 13:935-940. https://doi.org/10.18240/ijo.2020.06.12\u003c/li\u003e\n\u003cli\u003eKohnen T, Kook D (2009) Solving intraocular lens-related pigment dispersion syndrome with repositioning of primary sulcus implanted single-piece IOL in the capsular bag. J Cataract Refract Surg 35:1459-1463. https://doi.org/10.1016/j.jcrs.2009.05.005\u003c/li\u003e\n\u003cli\u003eRabie HM, Esfandiari H, Rikhtegar MH, Hekmat V (2018) Management of sulcus-fixated single-piece intraocular lens-induced pigmentary glaucoma with 3-piece IOL exchange. Int Ophthalmol 38:145-150. https://doi.org/10.1007/s10792-016-0435-9\u003c/li\u003e\n\u003cli\u003eNagata M, Matsushima H, Senoo T (2022) A case of pigment dispersion syndrome after placement of sulcus intraocular lens with 7-mm optic diameter after posterior capsule rupture. Case Rep Ophthalmol 13:1003-1009. https://doi.org/10.1159/000527750\u003c/li\u003e\n\u003cli\u003eSenthil S, Grover IG (2018) In-the-bag multifocal intraocular lens causing pigment dispersion and refractory secondary ocular hypertension. Indian J Ophthalmol 66:1339-1341. https://doi.org/10.4103/ijo.IJO_198_18\u003c/li\u003e\n\u003cli\u003eScheie HG (1957) Width and pigmentation of the angle of the anterior chamber; a system of grading by gonioscopy. AMA Arch Ophthalmol 58:510-512. https://doi.org/10.1001/archopht.1957.00940010526005 \u003c/li\u003e\n\u003cli\u003eMehta JS, Wilkins MR, Gartry DS (2005) Explantation of an acrylic Acrysof intraocular lens without wound enlargement. Acta Ophthalmol Scand 83:262-263. https://doi.org/10.1111/j.1600-0420.2005.00373.x\u003c/li\u003e\n\u003cli\u003eYamane S, Sato S, Maruyama-Inoue M, Kadonosono K (2017) Flanged intrascleral intraocular lens fixation with double-needle technique. Ophthalmology 124:1136-1142. https://doi.org/10.1016/j.ophtha.2017.03.036\u003c/li\u003e\n\u003cli\u003eKristianslund O, R\u0026aring;en M, \u0026Oslash;stern AE, Drolsum L (2017) Glaucoma and intraocular pressure in patients operated for late in-the-bag intraocular lens dislocation: a randomized clinical trial. Am J Ophthalmol 176:219-227. https://doi.org/10.1016/j.ajo.2017.01.026\u003c/li\u003e\n\u003cli\u003eShin DH, Birt CM, O\u0026apos;Grady JM, Kim C, Juzych MS, Lemon LC, Reed SY, Eliassi-Rad B (2001) Transscleral suture fixation of posterior chamber lenses combined with trabeculectomy. Ophthalmology 108:919-929. https://doi.org/10.1016/s0161-6420(01)00543-7 \u003c/li\u003e\n\u003cli\u003eZhang C, Palka C, Zhu D, Lai D, Winokur J, Shwani T, DeAngelis MM, Reynolds AL (2024) Clinical outcomes in scleral fixation secondary intraocular lens with Yamane versus suture techniques: a systematic review and meta-analysis. J Clin Med 13:3071. https://doi.org/10.3390/jcm13113071 \u003c/li\u003e\n\u003cli\u003eOkafor K, Vinod K, Gedde SJ (2017) Update on pigment dispersion syndrome and pigmentary glaucoma. Curr Opin Ophthalmol 28:154-160. https://doi.org/10.1097/ICU.0000000000000352\u003c/li\u003e\n\u003cli\u003eHong Y, Sun YX, Qi H, Zhou JC, Hao YS (2013) Pigment dispersion glaucoma induced by the chafing effect of intraocular lens haptics in Asian eyes. Curr Eye Res 38:358-362. https://doi.org/10.3109/02713683.2012.749502\u003c/li\u003e\n\u003cli\u003eMatsumoto Y, Johnson DH (1997) Trabecular meshwork phagocytosis in glaucomatous eyes. Ophthalmologica 211:147-152. https://doi.org/10.1159/000310782\u003c/li\u003e\n\u003cli\u003eEpstein DL, Freddo TF, Anderson PJ, Patterson MM, Bassett-Chu S (1986) Experimental obstruction to aqueous outflow by pigment particles in living monkeys. Invest Ophthalmol Vis Sci 27:387-395.\u003c/li\u003e\n\u003cli\u003eSakuma K, Hamanaka T, Matsuda A, Ishida M (2012) Acute onset secondary pigmentary glaucoma followed by second intraocular lens implantation in a patient with atopic dermatitis. J Clin Exp Ophthalmol 3:9. https://doi.org/10.4172/2155-9570.1000255\u003c/li\u003e\n\u003cli\u003eGottanka J, Johnson DH, Grehn F, L\u0026uuml;tjen-Drecoll E (2006) Histologic findings in pigment dispersion syndrome and pigmentary glaucoma. J Glaucoma 15:142-151. https://doi.org/10.1097/00061198-200604000-00011 \u003c/li\u003e\n\u003cli\u003eThe Advanced Glaucoma Intervention Study (AGIS): 7 (2000) The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 130:429-440. https://doi.org/10.1016/s0002-9394(00)00538-9\u003c/li\u003e\n\u003cli\u003eFukuchi T, Yoshino T, Sawada H, Seki M, Togano T, Tanaka T, Ueda J, Abe H (2013) The relationship between the mean deviation slope and follow-up intraocular pressure in open-angle glaucoma patients. J Glaucoma 22:689-697. https://doi.org/10.1097/IJG.0b013e318264b779\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\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":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Intraocular lens, Pigment dispersion syndrome, Intraocular pressure, Scleral fixation, Glaucoma surgery","lastPublishedDoi":"10.21203/rs.3.rs-6290360/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6290360/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Intraocular lens (IOL)-induced pigment dispersion syndrome (PDS) represents a significant clinical challenge. However, literature on treatment strategies based on intraocular pressure (IOP) is limited. In this retrospective comparative analysis, we analyzed patients with IOL-induced PDS who underwent surgical treatment, focusing on clinical outcomes and preoperative IOP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Japanese patients with glaucoma who underwent surgery for IOL-related PDS were divided into the IOL removal with scleral fixation of IOL (SFIOL) and glaucoma surgery groups. The SFIOL group was subdivided into the high- and low- pressure groups based on preoperative IOP. The main outcomes included mean IOP and cumulative success rates assessed using Kaplan–Meier curves.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: We analyzed 24 eyes (24 patients) in the SFIOL group and 15 (15 patients) in the glaucoma surgery group. In the SFIOL low-pressure group (preoperative IOP ≤24 mmHg), normal IOP was maintained, resulting in a postoperative 1-year cumulative 100% success rate; in the high-pressure group (preoperative IOP \u0026gt;24 mmHg), IOP was challenging to maintain even after IOL status improvement, resulting in a 24.2% success rate. In the glaucoma surgery group (median preoperative IOP 29 mmHg), the success criterion rate for 6 ≤ IOP ≤ 21 mmHg was 100%, and 49.2% for 6 ≤ IOP ≤ 14 mmHg.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: When preoperative IOP was maintained, normal pressure could be achieved by IOL status improvement. Additional glaucoma surgery was frequently required when preoperative IOP exceeded 24 mmHg. IOL and iris alignment should be corrected when preoperative IOP is maintained at \u0026lt; 24 mmHg.\u003c/p\u003e","manuscriptTitle":"Surgical outcomes of interventions for treating intraocular lens-induced secondary pigment dispersion syndrome: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 09:42:23","doi":"10.21203/rs.3.rs-6290360/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-19T12:09:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-17T13:15:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58261804419736582236743294636670291260","date":"2025-07-30T09:23:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-08T11:19:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329601846790498064600845142511368859467","date":"2025-05-13T07:22:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-27T11:13:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-24T06:33:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-24T06:31:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2025-03-23T22:41:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a3bc5b0d-e93b-4a48-81f1-3890965fc30c","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:32:43+00:00","versionOfRecord":{"articleIdentity":"rs-6290360","link":"https://doi.org/10.1007/s10792-025-03799-6","journal":{"identity":"international-ophthalmology","isVorOnly":false,"title":"International Ophthalmology"},"publishedOn":"2025-10-23 16:17:16","publishedOnDateReadable":"October 23rd, 2025"},"versionCreatedAt":"2025-04-17 09:42:23","video":"","vorDoi":"10.1007/s10792-025-03799-6","vorDoiUrl":"https://doi.org/10.1007/s10792-025-03799-6","workflowStages":[]},"version":"v1","identity":"rs-6290360","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6290360","identity":"rs-6290360","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}