Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy

Phase 4

• Conditions: Polypoidal Choroidal Vasculopathy; Exudative Age-related Macular Degeneration
• Interventions: Drug: ranibizumab

• Registration Number: NCT02976194
• Lead Sponsor: Pusan National University Hospital

Brief Summary

Changes of intraocular cytokines including vascular endothelial growth factor (VEGF) will be measured in recurrence of polypoidal choroidal vasculopathy (PCV) during treatment of ranibizumab.

Detailed Description

PCV is regarded as a subtype of age-related macular degeneration (ARMD), but has several different features such as polypoidal terminal of new vessels, and relative resistance to anti-VEGF treatment. Other cytokines then VEGF are thought to be associated with development and progression of the disease. The aim of the this study is to investigate intraocular cytokines related to recurrence of polypoidal choroidal vasculopathy. Aqueous humor will be sampled from the anterior chamber at baseline, after loading injections of ranibizumab and at recurrence. The concentration of various cytokines will be measured in the aqueous humor.

Study Timeline

• Study Start: 2016-11-22
• Study First Submitted: 2016-11-22
• Study First Submitted QC: 2016-11-28
• Study First Posted: 2016-11-29
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-08
• Last Update Posted: 2019-10-10
• Primary Completion: 2019-11
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Submacular PCV diagnosed based on branching neovascular networks having polypoidal dilatation in ICGA.
2. Presence of exudative changes involving the fovea in OCT
3. Decreased visual acuity to 20/320 - 20/40 to be primarily the results of PCV in the study eye.
4. Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form.

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Exclusion Criteria

1. Extramacular PCV.
2. Presence of pathologic changes blocking 50% or more area of the lesion in angiography.
3. Any anti-VEGF treatment in the study eye within 180 days of day 1.
4. Previous photodynamic therapy in the study eye.
5. History of intraocular surgery except uncomplicated cataract surgery performed before 90 days or more from day 1.
6. Presence of exudative ARMD requiring anti-VEGF treatment in the other eye.
7. Presence of other ocular disease that may compromise visual acuity in the study eye.
8. Uncontrolled systemic disease.
9. Active intraocular or periocular infection.
10. Active intraocular inflammation.
11. Hypersensitivity to ranibizumab or excipients.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pro-re-nata	ranibizumab	Ranibizumab 0.5mg is injected in to the vitreous cavity. An injection is given every 4 weeks three times, and then the patient will be followed up every 4 weeks. An addition injection is given as needed. Recurrence is defined as increase of exudative changes, or increase of 10% or more in central subfield macular thickness (CSMT) measured using optical coherence tomography. Aqueous humor is sampled from the anterior chamber before injection at baseline, 8 weeks and 20 weeks.

Primary Outcome Measures

Name	Time	Method
Changes of VEGF-A from 8 weeks to 20 weeks	8 weeks and 20 weeks	Intraocular concentration of VEGF-A is measured using multiplex immunoassay.

Secondary Outcome Measures

Name	Time	Method
Changes of cytokines from baseline to 8 weeks	baseline and 8 weeks	Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay.
Correlation between time to recurrence and cytokine concentration at baseline and 8 weeks.	baseline and 8 weeks	Time to recurrence is defined as number of weeks from 8 to recurrence. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between CSMT and cytokine concentration	baseline, 8 weeks and 20 weeks.	CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as increase of en exudative sign. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between choroidal thickness and cytokine concentration	baseline, 8 weeks and 20 weeks.	Choroidal thickness is thickness of the choroid measured at the foveal center using spectral-domain OCT. Increased choroidal thickness was reported to be related to poor response to anti-VEGF treatment. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between area of new vessels and cytokine concentration	baseline	Area of new vessels is measured in indocyanine green angiography (ICGA) obtained at baseline. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Changes of the other cytokines from 8 weeks to 20 weeks	8 weeks and 20 weeks	Intraocular concentration of the other cytokines including angiopoietin-1, interleukin-10 (IL-10), platelet-derived growth factor (PDGF) and placental growth factor (PlGF) is measured using multiplex immunoassay.
Correlation between vision changes and cytokine concentration changes	baseline and 24 weeks.	Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher score represents better functioning. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
Correlation between polyp closure and cytokine concentration changes	baseline and 8 weeks	Polyp closure is defined as disappearance of polypoidal terminal in new vessels assessed in ICGA at 8 weeks. The difference of cytokine concentration is assessed between the closed group and un-closed group using non-parametric analysis, or Mann-Whitney U test.

Trial Locations

Locations (2)

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Gyeongsangnam-do, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of