Clinical trial NCT05211804: Mechanisms of Retinal Revascularization and Clinical Indicators of Neovascular AMD Relapse
Official title: Mechanisms of Retinal Revascularization and Clinical Indicators of Neovascular AMD Relapse
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Sorlandet Hospital HF
Sponsor class: OTHER_GOV
First posted: 2022-01-27
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients will be recruited from nAMD patients in the clinic at Eye dep. Sorlandet Hospital Arendal.

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Neovascular changes during nAMD relapse assessed by the use of Optical Coherence Tomography Angiography
timeFrame: 12 months after inclusion of patients
Secondary outcomes:
measure: 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
timeFrame: 12 months after inclusion of patients
measure: Tear film of nAMD patients at different treatment stages to be collected by Schirmers test and further biochemically analysed
timeFrame: 12 months after inclusion of patients
measure: Blood samples of nAMD patients at different treatment stages will be collected in microtubes and further biochemically analysed
timeFrame: 12 months after inclusion of patients
Other outcomes:
Locations:
city: Arendal
country: Norway
facility: Sorlandet Hospital HF
state: Agder
Study officials:
affiliation: Sorlandet Hospital HF
name: Neil Lagali
role: PRINCIPAL_INVESTIGATOR
References: