Long-Term Remodeling Response in the Lamina Cribrosa Years after IOP Lowering by Suturelysis after Trabeculectomy

Objective: To measure the active remodeling of the lamina cribrosa (LC) years after IOP lowering by suturelysis. Design: Cohort study. Participants: Glaucoma patients were imaged 20 minutes after laser suturelysis following trabeculectomy surgery and at their follow-up appointment 1-4 years later (16 image pairs; 15 persons). Intervention: Non-invasive optical coherence tomography (OCT) imaging of the eye. Main Outcomes: Deformation calculated by correlating OCT scans of the LC immediately after IOP lowering by suturelysis and those acquired years later (defined as follow-up strain). Results: Mean LC follow-up strain in the anteroposterior direction (Ezz) was 14.0 ± 21.3% (mean, standard deviation, p=0.03), while the LC anterior border moved 60.9 ± 54.6 μm into the eye (p=0.0006) on long-term, maintained IOP lowering. Ezz at follow-up was 14 times larger than the direct Ezz response to IOP lowering by suturelysis. There was a significant association between larger LC anterior movement and greater Ezz (p=0.004) at follow-up. Thinner retinal nerve fiber layer (RNFL) at suturelysis was associated with greater follow-up Ezz (p=0.04). Worsening visual field indexes during follow-up were associated with greater LC widening (positive remodeling Eθθ, p=0.02). Eyes with a greater counterclockwise twist (positive Eθz) at suturelysis had greater reversal clockwise twist at follow-up (negative remodeling Eθz, p=0.007). Conclusion: Follow-up strains and LC border position changes measured years after IOP lowering are far larger than the immediate strain response and LC border movement response to IOP lowering and indicate dramatic remodeling of the LC anatomical structure caused by IOP lowering and glaucoma progression. The remodeling includes a substantial increase in LC thickness and movement into the eye. Eyes with greater direct strain response to IOP-lowering strains, greater glaucoma damage at suturelysis, and greater worsening of visual field at follow-up experienced greater remodeling. ### Competing Interest Statement The authors have no conflicting relationships related to the devices used in this research. Heidelberg Engineering donated the imaging device, but were not involved with data analysis or interpretation, nor with drafting of the manuscript. ### Clinical Trial NCT03267849 ### Funding Statement This research was funded in part by NIH NEI R01 02120 (Dr. Quigley), Brightfocus G2021012S, P30 01765 (Wilmer Institute Core Grant), Research to Prevent Blindness, the A. Edward Maumenee Professorship (Dr. Quigley), and BrightFocus. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The IRB of The Johns Hopkins Medicine gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors