Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Intraocular Cytokine Changes in Recurrence of Polypoidal Choroidal Vasculopathy

Conditions
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Exudative Age-related Macular Degeneration, Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Submacular PCV diagnosed based on branching neovascular networks having polypoidal dilatation in ICGA. Presence of exudative changes involving the fovea in OCT Decreased visual acuity to 20/320 - 20/40 to be primarily the results of PCV in the study eye. Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form. Exclusion Criteria: Extramacular PCV. Presence of pathologic changes blocking 50% or more area of the lesion in angiography. Any anti-VEGF treatment in the study eye within 180 days of day 1. Previous photodynamic therapy in the study eye. History of intraocular surgery except uncomplicated cataract surgery performed before 90 days or more from day 1. Presence of exudative ARMD requiring anti-VEGF treatment in the other eye. Presence of other ocular disease that may compromise visual acuity in the study eye. Uncontrolled systemic disease. Active intraocular or periocular infection. Active intraocular inflammation. Hypersensitivity to ranibizumab or excipients.

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pro-re-nata<br>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. | Drug: ranibizumab<br>* Ranibizumab 0.5mg is injected into the vitreous cavity through the pars plana using 30 gauge (or narrower) needle-attached syringe.<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of VEGF-A from 8 weeks to 20 weeks | Intraocular concentration of VEGF-A is measured using multiplex immunoassay. | 8 weeks and 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the other cytokines from 8 weeks to 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. | 8 weeks and 20 weeks | 
| Changes of cytokines from baseline to 8 weeks | Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay. | baseline and 8 weeks | 
| Correlation between time to recurrence and cytokine concentration at 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. | baseline and 8 weeks | 
| Correlation between vision changes and cytokine concentration changes | 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. | baseline and 24 weeks. | 
| Correlation between CSMT and cytokine concentration | 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. | baseline, 8 weeks and 20 weeks. | 
| Correlation between choroidal thickness and cytokine concentration | 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. | baseline, 8 weeks and 20 weeks. | 
| Correlation between area of new vessels and cytokine concentration | 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. | baseline | 
| Correlation between polyp closure and cytokine concentration changes | 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. | baseline and 8 weeks |