Aqueous Biomarker Levels in Diabetic Retinopathy and Diabetic Macular Edema

Study Overview
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Brief Summary
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The DRAGONS study is a non-interventional, prospective study that will characterize disease state biomarker (including cytokines, KKS metabolites, and cell adhesion molecules) levels from aqueous humor of subjects with various stages of diabetic retinopathy (DR) and diabetic macular edema (DME) as well as other retinal pathologies, and correlate a broad array of aqueous humor disease state biomarkers with DR severity, DME anti-vascular endothelial growth factor (VEGF) responsiveness, and other retinal pathologies.

Detailed Description
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The DRAGONS study is a non-interventional study investigating aqueous humor biomarker levels in patients with various stages of DR, DME and other retinal pathologies. Subjects will be included in the study if at least one eye meets any of the following criteria: Group 1 - eyes with treatment naive DR with or without DME Group 2 - eyes with DME that are incompletely responsive to anti-VEGF therapy Group 3 - eyes with various retinal conditions including eyes with DR and DME that are anti-VEGF responsive as well as non-exudative retinal pathologies such as epiretinal membrane and macular hole The study will consist of a single visit and a retrospective chart review. The study visit will consist of: Screening for eligibility; Aqueous humor collection; Blood collection; Optical coherence tomography; Optical coherence tomography angiography; Fundus photography; and Fluorescein angiography. Approximately 50 microliters (or more, up to 150 microliters) of aqueous fluid will be collected according to standard clinical procedures. Plasma and serum will be collected according to standard clinical procedures, with citrated plasma being specifically collected in a plastic tube.

Official Title
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Aqueous Biomarker Levels in Diabetic Retinopathy and Diabetic Macular Edema

Conditions
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Diabetic Retinopathy, Diabetic Macular Edema, Other Retinal Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Subjects with at least one of the following retinal conditions in at least one eye: Treatment naive diabetic retinopathy (group 1 only); Diabetic retinopathy with DME that is incompletely responsive to anti-VEGF therapy at principal investigators discretion with retinal thickening documented on OCT (group 2 only); Various retinal disease including but not limited to diabetic retinopathy without DME which has previously been treated, DME which has responded to anti-VEGF therapy, neovascular age-related macular degeneration, branch or central retinal vein occlusions, epiretinal membrane, or macular hole (group 3 only) Exclusion Criteria: Prior intraocular or subtenon steroid injection in the study eye within the prior 1 year of signing informed consent; Prior focal or grid laser photocoagulation in the study eye if within 90 days of signing informed consent; Prior panretinal photocoagulation in the study eye if within 90 days of signing informed consent; Intraocular or refractive surgery in the study eye within 90 days of signing informed consent; Systemic anti-VEGF treatment within 90 days of signing informed consent

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Eyes with treatment naive DR with or without DME | |
| Group 2<br>Eyes with DME that are incompletely responsive to anti-VEGF therapy | |
| Group 3<br>Eyes with various retinal conditions including eyes with DR and DME that is anti-VEGF responsive as well as non-exudative retinal pathologies such as epiretinal membrane and macular hole | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aqueous Humor Levels of VEGF-A |  | Baseline | 
| Aqueous Humor Levels of Plasma Kallikrein | Total Kallikrein (KLKB1), Active Kallikrein (pKal), Factor Xlla | Baseline | 
| Aqueous Humor Levels of Angiopoietin-2 |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aqueous Humor Levels of Additional Disease State Biomarkers | Angiopoietin-1, VEGF-D, IP-10, MCP-1, placental growth factor, platelet derived growth factor-B, TGF-β2, IL-1β, IL-6, IL-8, ICAM-1. | Baseline |