The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy

Study Overview
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Brief Summary
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A study investigating the ability of OCTA imaging technology to identify and analyze untreated type 1, 2, and 3 neovascular membrane lesions in treatment naive patients with exudative macular degeneration, as well as investigating the ability of the OCTA imaging technology to evaluate the treatment outcomes of Intravitreal Aflibercept Injection in neovascular lesions associated with macular degeneration. This study is utilizing a new, FDA approved, non-standard of care technology (OCT-Angiography by Optovue) to image and evaluate the treatment outcomes of using standard of care Intravitreal Aflibercept Injections for their approved use in patients diagnosed with neovascular AMD who are naive to previous Anti-VEGF therapies.

Detailed Description
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Prospective study of neovascular AMD subjects with type 1, 2, or 3 neovascularization that have not been treated with prior anti-VEGF therapy. Subjects will be scheduled for intravitreal aflibercept injection (IAI) at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per PI discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period. No injection will be given on the exit visit, week 52. OCT angiography and spectral domain OCT imaging will be performed at baseline and every 4 weeks thereafter The above procedures are standard of care for neovascular AMD subjects. As part of this study, these subjects will also undergo imaging of both eyes with OCTA at each visit. This is not standard of Care and is research. The only procedure that is being performed for research is the OCT-A. The injections and all other procedure are SOC based on physician discretion and clinical need. The investigators will not be modifying the dosage amounts or frequency. A subgroup of willing subjects will undergo OCT angiography every 2 weeks for the first 12 weeks. Indocyanine green angiography will be performed at baseline for all subjects to establish baseline subject population characteristics. Fluorescein angiography will be performed at baseline, week 12, and week 52 for efficacy monitoring. Detailed OCT angiography analysis will be performed to identify anatomical and morphological biomarkers of growth progression and disease activity. In addition to qualitative structural and morphological analysis, detailed quantitative OCT angiography analysis of the neovascular lesion using automated or manual capillary density maps and area calculation will be performed at each visit to determine the detailed microvascular response of neovascular complexes to IAI therapy.

Official Title
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The IAI-OCTA Study or; Microvascular Structure and Morphology of Neovascular Membranes in Age Related Macular Degeneration (AMD) After Intravitreal Aflibercept Injection (IAI) Therapy Using OCT-Angiography Analysis

Conditions
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Wet Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept Ophthalmic
* Device: optovue angiovue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is older than 50 years of age. Subject is willing to participate in the study and able to follow the study criteria and protocol. The study eye is treatment naive regarding treatment of neovascular AMD. Subject is willing and able to comply with clinic visits and study-related procedures. Subject is able to provide signed informed consent. Subject is able to understand and complete study-related questionnaires. The subject is not currently involved with any other clinical study. Best Corrected Visual Acuity (BCVA) with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse. Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography (FP). Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents. Prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted. Exclusion Criteria: Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins). Known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (e.g. Betadine Solution). Prior or current systemic anti-VEGF therapy. Pregnant or breast-feeding women. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly). Contraindication to pupillary dilation in study eye. Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements. Presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study. Previous therapeutic radiation in the region of the study eye. Prior retinal pigment epithelial (RPE) tear in study eye. Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days. Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months. Prior vitrectomy in the study eye. Presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IAI Treatment<br>Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per Primary Investigator (PI) discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT-angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period. | Drug: Aflibercept Ophthalmic<br>* IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC<br>Device: optovue angiovue<br>* FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.<br>* Other names: OCTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan. | Area of the neovascular lesion (in millimeters^2) | Week 24 | 
| Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan. | Area of the neovascular lesion (in millimeters^2) | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change | patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters). | Baseline, Week 24 | 
| Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change | patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters). | Week 24, Week 52 | 
| Mean Best Corrected Visual Acuity (BCVA) | Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity. | Week 24 | 
| Mean Best Corrected Visual Acuity (BCVA) | Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity. | Week 52 |