Clinical trial NCT04853355: Non-Responsive Diabetic Macular Edema and Spironolactone
Official title: Non-Responsive Diabetic Macular Edema in Patients With Pachychoroid and Choroidal Hyperpermeability.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Diabetic Maculopathy
Keywords: spironolactone
anti-VEGF injections
aflibercept
Eylea
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2021-04-21
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, non-randomized, pilot study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion:

1. 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).
2. 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.
3. Visual Acuity of 20/25 to 20/400 at screening and baseline visits using an autorefractor or Early Treatment Diabetic Retinopathy Study (ETDRS).
4. 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:

1. Exudative maculopathies due to myopic choroidal degeneration, histoplasmosis, trauma, and specifically, the presence of angioid streaks.
2. Myocardial infarction or cerebrovascular accident within the last 6 weeks
3. Previous vitrectomy
4. Hypokalemia
5. Optic neuropathy
6. Traction maculopathies
7. Allergies to fluorescein and indocyanine, dilating agents, spironolactone, triamcinolone or anti-VEGF medications

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Primary outcomes:
measure: Proportion of eyes with complete reabsorption of intraretinal fluid
timeFrame: 1 year
measure: Macular Edema - Central Subgroup Thickening
timeFrame: 1 year
measure: Macular Edema - Volume
timeFrame: 1 year
measure: Vision, best corrected, logMAR units
timeFrame: 1 year
Secondary outcomes:
measure: Extrafoveal exudation (nCST)
timeFrame: 1 year
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Mark H Nelson, MD MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim DY, Lee JY, Lee EK, Kim JY. COMPARISON OF VISUAL/ANATOMICAL OUTCOMES AND RECURRENCE RATE BETWEEN ORAL SPIRONOLACTONE AND PHOTODYNAMIC THERAPY FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY. Retina. 2020 Jun;40(6):1191-1199. doi: 10.1097/IAE.0000000000002507.