Ranibizumab Versus Low-fluence Photodynamic Therapy in the Treatment of Chronic Central Serous Chorioretinopathy

Prospective Study on the Efficacy and Safety of Intravitreal Ranibizumab Versus Low-fluence Photodynamic Therapy in the Treatment of Chronic Central Serous Chorioretinopathy

The purpose of this study is to compare the efficacy and safety of intravitreal ranibizumab injection versus low-fluence PDT in the treatment of chronic CSC.

Study Overview

• Status: Completed
• Conditions: Chronic Central Serous Chorioretinopathy
• Intervention / Treatment: Drug: Verteporfin; Drug: ranibizumab

Detailed Description

Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neurosensory retina. The pathophysiology of CSC is not certain and various theories are proposed including impaired function of retinal pigment epithelium (RPE), choroidal ischemia and choroidal hyperpermeability leading to RPE damage. Acute CSC with monofocal or paucifocal changes of RPE usually shows spontaneous resolution and has a favorable visual outcome. Chronic CSC is characterized by multifocal or diffuse decompensation of RPE associated with persistent detachment of neurosensory retina. This might lead to cystoid macular degeneration, foveal atrophy and damage to the foveal photoreceptor layer, consequently resulting in irreversible significant visual loss. Photodynamic therapy (PDT) was proposed for the treatment of chronic CSC. Modified parameters of PDT such as shortening of the time of laser emission and reduction of a total light energy have been suggested to reduce the irreversible damages induced by conventional PDT. Recently, intravitreal injection of antibody to vascular endothelial growth factor(VEGF) was proposed as a new treatment option based on the effect of anti-permeability. Several reports demonstrated acceptable outcomes after intravitreal bevacizumab injection, one of anti-VEGF agent. But the clinical results with ranibizumab are not reported yet. The purpose of this study is to compare the efficacy and safety of intravitreal ranibizumab injection versus low-fluence PDT in the treatment of chronic CSC.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seoul, Gyeonggi-do, Korea, Republic of
      • • Department of Ophthalmology, Seoul National University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. best-corrected visual acuity (BCVA) between 0.0 and 1.0 logarithm of the minimal angle of resolution (logMAR)
2. presence of subfoveal fluid persisting for 3 months or more on optical coherence tomography (OCT)
3. presence of leakage and multifocal/diffuse RPE decompensation on fluorescein angiography (FA)
4. choroidal vascular hyperpermeability and abnormal dilation of choroidal vasculature on indocyanine angiography (ICGA)

Exclusion Criteria:

1. previous treatment, such as laser photocoagulation, PDT, intravitreal injection of steroid or anti-VEGF agent
2. evidence of choroidal neovascularization
3. any other ocular diseases that could affect visual acuity
4. systemic steroid treatment in the previous 12 months
5. media opacity such as cataract that could interfere with adequate acquisition of OCT, FA and ICGA images

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-fluence PDT with Verteporfin; Half the regular laser fluence PDT(Visudyne®; Novartis); a total light energy of 25J/cm2, a light dose rate of 300mW/cm2. If subretinal fluid was sustained after primary treatment, rescue treatment(ranibizumab injection) was considered	Drug: Verteporfin; a 6mg/m2 infusion of verteporfin(Visudyne; Novartis)over 10 minutes followed by laser delivery; Other Names: Visudyne
Active Comparator: Ranibizumab; Consecutive Intravitreal injection of ranibizumab(Lucentis®, Novartis) 0.5mg/0.05ml for the first 3 months. If subretinal fluid was sustained after primary treatment, rescue treatment(low-fluence photodynamic therapy) was considered	Drug: ranibizumab; Consecutive intravitreal injection of ranibizumab(Lucentis®, Novartis) 0.5mg/0.05ml for the first 3 months; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Achieved Complete Resolution of Subretinal Fluid on OCT Without Rescue Treatment	number of participants who achieved complete resolution of subretinal fluid on OCT without rescue treatment until the end of the study	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in logMAR BCVA	the changes from baseline in logMAR BCVA throughout the follow-up period	12 months
Change From Baseline in Central Foveal Thickness on OCT	the change from baseline in central foveal thickness measured by OCT throughout the follow-up period	12 months
Number of Participants With Leakage on Fluorescein Angiography	number of participants who showed fluorescein leakage after primary or rescue treatment throughout the follow-up period	12 months
Change From Baseline in Choroidal Hyperpermeability on Indocyanine Green Angiography	change from baseline in the status of choroidal perfusion and hyperpermeability on indocyanine green angiography throughout the follow-up period	12 months
Number of Participants Who Underwent Rescue Treatment	number of participants who underwent rescue treatment: ranibizumab injections for the low-fluence PDT group and low-fluence PDT for the ranibizumab group	12 months
Number of Participants With Adverse Event	number of participants with adverse event throughout the follow-up period including procedure and drug-related adverse events	12 months

Collaborators and Investigators

• Sponsor: Jang Won Heo
• Collaborators: Novartis Korea Ltd.
• Investigators: Principal Investigator: Jang Won Heo, Professor, Seoul National University Hospital

Publications and helpful links

General Publications

• Bae SH, Heo JW, Kim C, Kim TW, Lee JY, Song SJ, Park TK, Moon SW, Chung H. A randomized pilot study of low-fluence photodynamic therapy versus intravitreal ranibizumab for chronic central serous chorioretinopathy. Am J Ophthalmol. 2011 Nov;152(5):784-92.e2. doi: 10.1016/j.ajo.2011.04.008. Epub 2011 Jul 13.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: March 25, 2011
• First Submitted That Met QC Criteria: March 27, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): May 27, 2013
• Last Update Submitted That Met QC Criteria: April 5, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Ranibizumab; Photodynamic therapy; Chronic central serous chorioretinopathy
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Central Serous Chorioretinopathy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Photosensitizing Agents; Dermatologic Agents; Ranibizumab; Verteporfin
• Other Study ID Numbers: NOV001