Mechanisms of Retinal Revascularization and Clinical Indicators of Neovascular AMD Relapse

NCT05211804 | Completed

• 1 other identifier: 21-06505
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Age-related macular degeneration (AMD) is a chronic and progressive eye disease and is one of the leading causes of vision impairment globally. AMD is referred to as either the dry or the wet type, where the wet type (also called neovascular-AMD or nAMD) is a later stage of the disease with neovascularization and retinal edema being the main attributes. This will usually cause subacute distortion or loss of central vision in patients. Since 2004, a successful treatment alternative for nAMD has been ocular injections with anti-VEGF (anti-Vascular Endothelial Growth Factor), causing the neovascularization and edema to regress and vision to improve. However, injections have to be repeated, usually requiring 8 injections or more during the first year of treatment. This can cause both a risk for serious adverse effects and is a significant financial drain on health care resources. Patients undergoing treatment are at risk for retinal edema recurrence. The time interval tolerated between injections is individual, and the accepted treatment strategy of today is to gradually, in a stepwise manner, increase the interval between injections. For some patients this extension is well tolerated, but for many patients relapse of proliferations and retinal edema will recur. With state-of-the-art technology OCT-A (optical coherence tomography-angiography) in combination with the clinically, well established examination method of OCT (optical coherence tomography), the project group will study the phenotypic vessel and tissue changes that occur in between injections. Furthermore, the investigators will measure cytokines, chemokines and growth factors in blood samples and the tear film during different treatment stages to see if any single factor is prognostic for poorer response to treatment or relapse. In the short term, the project group hope that the knowledge gained from this project could lead to a better understanding of the mechanisms behind nAMD neovascular relapse and to apply this to routine screening in the clinics. In the longer term, the project group hope that elucidating the physical mechanisms and molecular changes could enable new targeted therapies to be developed. Aim 1: To characterize the phenotype of vessels in relapsing nAMD patients and compare to those without relapse using OCT-A imaging Aim 2: To investigate retinal edema and choroidal thickness in correlation with neovascular changes of relapsing nAMD Aim 3: To measure cytokines, chemokines and growth factors in the tear film before and during treatment with anti-VEGF for nAMD With our main hypothesis being: Relapse of nAMD in patients occurs principally through reconfiguration and vasodilatation of persistent non-regressed vessels following anti-VEGF treatment, while fully regressed vessels remain dormant

Conditions

Wet Macular Degeneration

Keywords

age related macular degeneration; age-related macular degeneration; wet age related macular degeneration; wet age-related macular degeneration; Optical Coherence Tomography Angiography; Optical Coherence Tomography; anti vascular endothelial growth factor; neovascular age related macular degeneration; neovascular age-related macular degeneration

Outcome Measures

Primary Outcomes (1)

• Neovascular changes during nAMD relapse assessed by the use of Optical Coherence Tomography Angiography

  Images gathered from OCTA imaging will be collected and vessel phenotype will be compared between different treatment stages to identify how vessels develop over time. The attributes that will be measured are feeder vessel thickness and to assess if new vessels develop "de novo" or by using old vessel pathways. The investigators intend to describe these findings and there are no planned metric measurements. This outcome is considered a descriptive, qualitative outcome.

  12 months after inclusion of patients

Secondary Outcomes (3)

• Choroidal thickness in nAMD patients undergoing treatment with anti-VEGF will be measured by the use of a caliper tool (metric scale) in the Optical Coherence Tomography software

  12 months after inclusion of patients

• Tear film of nAMD patients at different treatment stages to be collected by Schirmers test and further biochemically analysed

  12 months after inclusion of patients

• Blood samples of nAMD patients at different treatment stages will be collected in microtubes and further biochemically analysed

  12 months after inclusion of patients

Study Arms (2)

Treatment-naïve

15 patients not previously receiving anti-VEGF treatment for nAMD.

Drug: Ophthalmic Drugs

Undergoing treatment

15 patients already undergoing treatment with anti-VEGF for nAMD.

Drug: Ophthalmic Drugs

Interventions

Ophthalmic Drugs DRUG

Patients will receive the same treatment as if not a part of the project

Also known as: Aflibercept, Bevacizumab, Ranibizumab

Treatment-naïve; Undergoing treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients will be recruited from nAMD patients in the clinic at Eye dep. Sorlandet Hospital Arendal.

You may qualify if:

• Patients have to be 18 years or older
• Newly diagnosed nAMD (group 1) or nAMD treatment for at least 1 year (group 2), both with typical neovascular findings on OCT-A
• Patients with acceptable travel distance to the hospital
• Patients accepting to be part of the study

You may not qualify if:

• Other non-AMD macular disorders
• A spherical equivalent of -6 diopters or less
• Opacities of the visual axis; Changes of the cornea, anterior chamber, lens or vitreous cavity causing image acquisition artefacts
• Patients not able to attend extra controls due to age, illnesses or other factors
• Contraindications of intraocular injection therapy; Active ocular or periocular infection, active and serious intraocular inflammation, hypersensitivity to the drug or recent stroke / heart attack

Sponsors & Collaborators

• Sorlandet Hospital HF: lead

Study Sites (1)

Sorlandet Hospital HF

Arendal, Agder, 4838, Norway

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Tear film on Schirmers test stored in microtubes at -80°C for biochemical analyses. Blood plasma stored in microtubes at -80°C for biochemical analyses.

MeSH Terms

Conditions

Wet Macular Degeneration; Macular Degeneration

Interventions

sulphadicramide; aflibercept; Bevacizumab; Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Neil Lagali

  Sorlandet Hospital HF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 27, 2022
• Study Start: February 8, 2022
• Primary Completion: May 21, 2024
• Study Completion: May 21, 2024
• Last Updated: June 5, 2024

Record last verified: 2024-03

Locations

NO (1)