Molecular Background of Endothelial Cell Loss in Patients With Phakic Intraocular Lenses: a Tear and Aqueous Humour Analysis Study (MoBack)

Molecular Background of Endothelial Cell Loss in Patients With Phakic Intraocular Lenses (MoBack-ECL): a Tear and Aqueous Humour Analysis Study

Rationale: The number of highly myopic patients is increasing. Especially in East and Southeast Asia, up to 90% of adolescents are currently myopic. Long-term treatment of high myopia can be obtained by three types of surgery: laser refractive surgery, phakic intraocular lens (pIOL) implantation, and refractive lens exchange Implantation with a pIOL is the preferred treatment for high myopes, resulting in increasing patient numbers implanted due to the increasing numbers of patients with high myopia.

Long-term results show that implantation of a pIOL induces an accelerated decrease in corneal endothelial cells (EC). Although some risk factors for increase EC loss have been identified, the underlying mechanism is currently unknown. It is hypothesized that the aqueous flow in the anterior segment of the eye (i.e. anterior chamber) is disturbed, causing an altered nutritional flow in the anterior chamber. Another hypothesis is that the pIOL causes chronic subclinical inflammation in the anterior chamber resulting in increased EC loss. Currently there is insufficient proof to confirm or reject either hypothesis. If one of these hypotheses can be confirmed, it is likely to induces significant changes in clinical practice.

Objective: The primary objective of the study is to explore the role of inflammation in the anterior chamber on endothelial cell loss in patients implanted with iris-fixated pIOLs. The secondary objective is to identify whether there is a correlation between biomarkers in aqueous humour and biomarkers in tears, both related to the accelerated progression of EC loss.

Study design: Two strategies are incorporated in the design of this study. The first part will retrospectively evaluate EC loss in patients with iris-fixated (IF) phakic intraocular lenses (pIOLs). The second part is prospective and will compare EC measurements, cytokines in aqueous humour and in tears from patients scheduled for IF-pIOLs explantation and compare them to patients with routine cataract surgery.

Study population: Patients over 18 years of age, undergoing regular cataract surgery, and patients undergoing pIOL explantation in combination with cataract surgery. A total number of 126 patients is needed, equally divided over two groups.

Study Overview

• Status: Recruiting
• Conditions: Cataract; Phakic Intraocular Lens Explantation
• Intervention / Treatment: Procedure: Phakic intraocular lens (pIOL) explantation

• Study Type: Observational
• Enrollment (Estimated): 126

Contacts and Locations

• Study Contact: Name: Christian Bertens; Phone Number: +31 (0)43 388 1847; Email: christian.bertens@mumc.nl
• Study Contact Backup: Name: Frank van den Biggelaar, PhD; Phone Number: +31 (0)43 387 5342; Email: f.vanden.biggelaar@mumc.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Recruiting
      • Maastricht University Medical Centre
      • Contact: Frank van den Biggelaar, PhD; Phone Number: 0031433877377; Email: f.vanden.biggelaar@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Two groups will be included to compare endothelial cell loss due to inflammation in affected (i.e. iris-fixated [IF] phakic intraocular lens [pIOL] implanted) versus healthy (i.e. scheduled for regular cataract surgery) eyes.

Description

Inclusion Criteria:

• Age over 18
• Cataract in one or both eyes, or indication for pIOL explantation
• Informed and having given informed consent.

Exclusion Criteria:

• Insufficient understanding of the Dutch language to comply with study procedures
• Inability to complete follow-up or comply with study procedures
• Non-routine cataract surgery
• Cognitive or behavioral conditions that might interfere with surgery
• Patients with ocular comorbidities such as
• Women who are pregnant or nursing their child
• Immune-compromised patients (e.g., systemic corticosteroid use, leukaemia)
• Factors that increase the risk of complicated surgery

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Phakic intraocular lens (pIOL) explantation; Patients with pIOLs where a combined pIOL explantation and cataract surgery is needed.	Procedure: Phakic intraocular lens (pIOL) explantation; Phakic intraocular lens (pIOL) explantation is a surgical procedure to remove the pIOL which needs to be done after cataract formation. Cataract extraction is a surgical procedure to remove a lens in the eye that has become cloudy over time, affecting vision in that eye.; Other Names: Cataract extraction
Cataract extraction; Healthy control group of patients scheduled for regular cataract surgery without comorbidities affecting an immune response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in pro- inflammatory cytokine levels between patients undergoing a pIOL explantation in combination with a cataract surgery compared to patients only undergoing cataract surgery in aqueous humour.	Cytokines of interest are IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, MMP9. Detection will be in pg/mL.	up to 12 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between inflammatory biomarkers (cytokines) in the aqueous humour and in tears	The following assay will be used: MSD multiplex pro-inflamatory kit.	up to 12 months after surgery
Progress of EC loss after combined IF-pIOL explantation and cataract surgery compared to cataract surgery as a single procedure.	Progress will be measured with non-contact specular microscopy which will be the same for all patients.	up to 12 months after surgery

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lens Diseases; Cataract
• Other Study ID Numbers: NL70342.068.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No