Non-Responsive Diabetic Macular Edema and Spironolactone

Study Overview
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Brief Summary
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Diabetic patients with macular edema and choroidal hyperpermeability (as manifested as a thick choroid on OCT (optical coherence tomography) and ICG hyperfluorescence on ICG) unresponsive to anti-VEGF (vascular endothelial growth factor) and steroid injections will be treated with spironolactone in addition to the continued treatment of anti-VEGF injections, specifically aflibercept (Eylea).

Detailed Description
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This is a non-randomized, prospective study of 10 patients referred during the years 2018 to 2020 with the diagnosis of Diabetic Macular Edema. Each patient was noted to have pachychoroid, choroidal hyperpermeability, and most important resistant to multiple anti-VEGF and steroid intravitreal injections, and have moderate vision loss. In addition, despite the fact that we use anti-VEGF medications, we do not know the levels of VEGF in the eye, nor do we have an explanation for the inability to respond to these drugs. This study will determine the degree of VEGF concentrations, response to anti-VEGF treatments, and determine biomarkers of inflammation as a means for explaining the cause of treatment resistance. Subsequently, another pathological process will be treated with spironolactone to see if the degree of contribution of choroidal hyperpermeability to the exudative process.

Official Title
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Non-Responsive Diabetic Macular Edema in Patients With Pachychoroid and Choroidal Hyperpermeability.

Conditions
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Diabetic Maculopathy

Intervention / Treatment
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* Drug: Spironolactone 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion: Presence of persistent Diabetic cystoid macular edema despite course of anti-VEGF injections and intraocular steroids. At the time of study baseline, the patients must be on q4 week intravitreal anti-VEGF medications and have failed (poor response - less than 50% decrease in macular central subfield thickness (CST) and volume) with intravitreal steroids (triamcinolone acetonide or dexamethasone implant). Evidence of pachychoroid (choroid greater than 300 microns on OCT - EDI) with pachyvessels on OCT or OCTA. In addition, ICG (Indocyanine Green Angiogram) must show evidence of hyperfluorescence. Visual Acuity of 20/25 to 20/400 at screening and baseline visits using an autorefractor or Early Treatment Diabetic Retinopathy Study (ETDRS). IOP ≤ 25 mmHg - Patients that screen fail due to elevated IOP ˃25 mmHg may rescreen once IOP is treated and within normal limits (≤25 mmHg). Exclusion: Exudative maculopathies due to myopic choroidal degeneration, histoplasmosis, trauma, and specifically, the presence of angioid streaks. Myocardial infarction or cerebrovascular accident within the last 6 weeks Previous vitrectomy Hypokalemia Optic neuropathy Traction maculopathies Allergies to fluorescein and indocyanine, dilating agents, spironolactone, triamcinolone or anti-VEGF medications -

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, non-randomized, pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spironolactone Treatment<br>Patients with non-responsive Diabetic Macular Edema will be treated with Spironolactone in addition to the regular course of monthly aflibercept (Eylea). | Drug: Spironolactone 50 mg<br>* Add Spironolactone 50 mg to previous regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eyes with complete reabsorption of intraretinal fluid |  | 1 year | 
| Macular Edema - Central Subgroup Thickening |  | 1 year | 
| Macular Edema - Volume | Macular volume | 1 year | 
| Vision, best corrected, logMAR units |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extrafoveal exudation (nCST) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aflibercept, spironolactone, anti-VEGF injections, Eylea