Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry

Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry | 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 Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry Helia Ashourizadeh, Joshua B. Gilbert, Nicole Grinspan, William C. Kearney, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5505014/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Objective To evaluate the association between cataract surgery (CS) and risk of conversion from dry age-related macular degeneration (dAMD) to neovascular AMD (nvAMD), and to identify factors associated with conversion. Design Population-based retrospective time-to-event study Subjects Patients aged ≥55 years with early or intermediate dAMD and phakic status at baseline. Eyes with a history of CS, a prior diagnosis of nvAMD, or prior anti–vascular endothelial growth factor (anti-VEGF) therapy before cohort entry were excluded. Eyes that underwent CS were classified as exposed; those without CS during the study period were nonexposed. Methods Eyes were propensity score matched 1:1 on age, sex, race, and ethnicity, laterality, AMD stage, and smoking status. CS was modeled as a time-varying exposure. We used Cox proportional hazards regression to estimate the hazard of conversion to nvAMD over the 7-year study period. Main Outcome Measures Conversion from dAMD to nvAMD between exposed and nonexposed cohorts Results After matching, 40,053 eyes were included in each exposed and nonexposed cohort (total N = 80,106 eyes). CS was associated with a higher risk of nvAMD conversion (hazard ratio [HR] = 1.22; 95% CI, 1.16–1.30; P < 0.001). Time-varying analysis demonstrated that this association was strongest early in follow-up (HR ≈ 2.5 in year 1) and declined steadily, reaching non-significance (HR ≈ 1.0) by year 4. At year 6, the cumulative incidence of nvAMD was 17.7% in the exposed cohort versus 15.2% in the nonexposed cohort. Baseline AMD stage moderated the effect of CS, with weaker effects of CS for intermediate AMD (Interaction HR = 0.82, 95% CI, 0.78-0.92). Conclusions CS was associated with a modestly increased overall rate of conversion from dAMD to nvAMD; however, the time-dependent pattern suggests that the observed association likely reflects increased surveillance or unrecognized pre-existing nvAMD rather than a sustained biological effect of surgery. The absolute risk difference was small (~3.3% over six years). These findings support careful perioperative evaluation in dAMD patients but do not implicate CS as a long-term driver of neovascular conversion. Ophthalmology Age-Related Macular degeneration cataract cataract surgery dry AMD neovascular AMD Figures Figure 1 Figure 2 Full Text Additional Declarations The authors declare potential competing interests as follows: Helia Ashourizadeh: None; Joshua Gilbert: None; Nicole Grinspan: None; Connor Ross: None; William C. Kearney: None; Tobias Elze: Grant support – Genentech Inc.; Joan W. Miller: Grant support – National Eye Institute, Massachusetts Eye and Ear Clinical Data Science Fund, Lowy Medical Research Institute; Consultant – Genentech/Roche, Heidelberg Engineering, KalVista Pharmaceuticals, ONL Therapeutics, Sunovion; Research support – Aptinyx, Inc., Heidelberg Engineering, KalVista Pharmaceuticals, ONL Therapeutics, Sunovion, Valeant Pharmaceuticals/Mass. Eye and Ear; Patents – ONL Therapeutics, Valeant Pharmaceuticals/Mass. Eye and Ear; Stock – Aptinyx, Inc.; Alice Lorch: Grant support – Massachusetts Eye and Ear Clinical Data Science Fund; Grayson W. Armstrong: Consultant - Ocular Technologies Inc, McKinsey & Company, Kriya Therapeutics, Xenon Ophthalmics, Chart Biopsy, Dynamed, Optomed, Genentech Supplementary Files Supplemental1.pdf Supplental 1 Supplemental2.pdf Supplemental 2 Table1.docx Table1.docx Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5505014","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":382436616,"identity":"b815274f-a805-41e1-a380-2d9174e9799c","order_by":0,"name":"Helia Ashourizadeh","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Helia","middleName":"","lastName":"Ashourizadeh","suffix":""},{"id":382436617,"identity":"f78dae78-c786-4e3f-8c72-5a106e372e91","order_by":1,"name":"Joshua B. 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(A) Overall survival functions. (B–D) Survival functions stratified by AMD stage (B), laterality (C), and age (D). “Exposed” denotes post-cataract surgery eye time; “nonexposed” denotes time prior to cataract surgery or in eyes that never underwent cataract surgery. Note: (D) Curves are shown at representative ages corresponding to the cohort mean ±1 standard deviation, holding other covariates constant. The shaded area indicates the 95% confidence interval.\u003c/p\u003e","description":"","filename":"Unknown.png","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/2dcc6916184100fb7054c482.png"},{"id":104106201,"identity":"a1f41348-389d-4efd-b546-443809604255","added_by":"auto","created_at":"2026-03-06 22:01:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":199153,"visible":true,"origin":"","legend":"\u003cp\u003eTime-varying hazard ratio of neovascular AMD conversion associated with cataract surgery over the follow-up period (point estimates and 95% confidence intervals)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/a07c8d3523cd83ed7590d623.png"},{"id":104408804,"identity":"368f2e16-644e-4bd5-ad93-a09874ea4f06","added_by":"auto","created_at":"2026-03-11 12:43:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":634692,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscriptcleancopy02162026.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2_covered_7d94715f-406f-4d5b-8230-af8e8efaa9c7.pdf"},{"id":104106202,"identity":"4845bceb-7533-41b8-9a50-d6a9deef3f3b","added_by":"auto","created_at":"2026-03-06 22:01:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":95703,"visible":true,"origin":"","legend":"\u003cp\u003eSupplental 1\u003c/p\u003e","description":"","filename":"Supplemental1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/9de10e4eda3ed03b93e65901.pdf"},{"id":104106204,"identity":"f7e3ace6-8cd3-40aa-accc-f66b3fe1c259","added_by":"auto","created_at":"2026-03-06 22:01:37","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":249641,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental 2\u003c/p\u003e","description":"","filename":"Supplemental2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/ee26dd92f5e5a0fb9a047544.pdf"},{"id":104403288,"identity":"98e512c8-3f0d-4c99-9814-de8cdc75dc02","added_by":"auto","created_at":"2026-03-11 12:17:56","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":18204,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/036735a3abecdcf4ef7eacbb.docx"},{"id":104403626,"identity":"ddeb95a1-ec0f-4d8f-adc5-3198c874ed0d","added_by":"auto","created_at":"2026-03-11 12:18:43","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":18204,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5505014/v2/235f46cb8e4e84f99ef22c74.docx"}],"financialInterests":"The authors declare potential competing interests as follows: Helia Ashourizadeh: None; Joshua Gilbert: None; Nicole Grinspan: None; Connor Ross: None; William C. Kearney: None; Tobias Elze: Grant support – Genentech Inc.; Joan W. Miller: Grant support – National Eye Institute, Massachusetts Eye and Ear Clinical Data Science Fund, Lowy Medical Research Institute; Consultant – Genentech/Roche, Heidelberg Engineering, KalVista Pharmaceuticals, ONL Therapeutics, Sunovion; Research support – Aptinyx, Inc., Heidelberg Engineering, KalVista Pharmaceuticals, ONL Therapeutics, Sunovion, Valeant Pharmaceuticals/Mass. Eye and Ear; Patents – ONL Therapeutics, Valeant Pharmaceuticals/Mass. Eye and Ear; Stock – Aptinyx, Inc.; Alice Lorch: Grant support – Massachusetts Eye and Ear Clinical Data Science Fund; Grayson W. Armstrong: Consultant - Ocular Technologies Inc, McKinsey \u0026 Company, Kriya Therapeutics, Xenon Ophthalmics, Chart Biopsy, Dynamed, Optomed, Genentech","formattedTitle":"\u003cp\u003eCataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Massachusetts Eye and Ear Infirmary","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Age-Related Macular degeneration, cataract, cataract surgery, dry AMD, neovascular AMD","lastPublishedDoi":"10.21203/rs.3.rs-5505014/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5505014/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the association between cataract surgery (CS) and risk of conversion from dry age-related macular degeneration (dAMD) to neovascular AMD (nvAMD), and to identify factors associated with conversion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePopulation-based retrospective time-to-event study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients aged ≥55 years with early or intermediate dAMD and phakic status at baseline. Eyes with a history of CS, a prior diagnosis of nvAMD, or prior anti–vascular endothelial growth factor (anti-VEGF) therapy before cohort entry were excluded. Eyes that underwent CS were classified as exposed; those without CS during the study period were nonexposed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEyes were propensity score matched 1:1 on age, sex, race, and ethnicity, laterality, AMD stage, and smoking status. CS was modeled as a time-varying exposure. We used Cox proportional hazards regression to estimate the hazard of conversion to nvAMD over the 7-year study period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMain Outcome Measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConversion from dAMD to nvAMD between exposed and nonexposed cohorts\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter matching, 40,053 eyes were included in each exposed and nonexposed cohort (total N = 80,106 eyes). CS was associated with a higher risk of nvAMD conversion (hazard ratio [HR] = 1.22; 95% CI, 1.16–1.30; \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.001). Time-varying analysis demonstrated that this association was strongest early in follow-up (HR ≈ 2.5 in year 1) and declined steadily, reaching non-significance (HR ≈ 1.0) by year 4. At year 6, the cumulative incidence of nvAMD was 17.7% in the exposed cohort versus 15.2% in the nonexposed cohort. Baseline AMD stage moderated the effect of CS, with weaker effects of CS for intermediate AMD (Interaction HR = 0.82, 95% CI, 0.78-0.92).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCS was associated with a modestly increased overall rate of conversion from dAMD to nvAMD; however, the time-dependent pattern suggests that the observed association likely reflects increased surveillance or unrecognized pre-existing nvAMD rather than a sustained biological effect of surgery. The absolute risk difference was small (~3.3% over six years). These findings support careful perioperative evaluation in dAMD patients but do not implicate CS as a long-term driver of neovascular conversion.\u003c/p\u003e","manuscriptTitle":"Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-03-06 22:01:32","doi":"10.21203/rs.3.rs-5505014/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2024-11-25 15:38:45","doi":"10.21203/rs.3.rs-5505014/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"84507291-fd68-4693-a2fa-d95c436954be","owner":[],"postedDate":"March 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":64079340,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2024-11-25T15:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-06 22:01:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-5505014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5505014","identity":"rs-5505014","version":["v2"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}