Selective Retina Therapy With 'R:GEN' in Patients With Central Serous Chorioretinopathy

A Prospective, Multi-center, Randomized, Double-blinded (Subject & Independent Efficacy Evaluator), Comparative Clinical Study to Evaluate the Efficacy and Safety of SRT (Selective Retina Therapy) With 'R:GEN' in Patients With Central Serous Chorioretinopathy

The purpose of this clinical study is to evaluate the efficacy and safety of selective retina therapy (SRT) using R:GEN, an approved laser device, in patients with central serous chorioretinopathy.

Study Overview

• Status: Completed
• Conditions: Central Serous Chorioretinopathy
• Intervention / Treatment: Device: R:GEN Selective Retina Therapy

Detailed Description

In this study, treatment effect of each group will be evaluated by follow-up once a month of both study group and control group other than the 2nd month until 6 months following the first procedure.

For the primary efficacy evaluation, the percentage of subjects who show complete removal of sub-retinal fluid (SRF) in Optical Coherence Tomography (OCT) results will be evaluated in the study group, before SRF therapy and at 3 months after therapy, and in control group, before sham procedure using R:GEN and at 3 months after therapy. In addition, for secondary efficacy evaluation, major symptoms of central serous chorioretinopathy will be evaluated at 3 and 6 months including changes in best corrected visual acuity (BCVA) on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the degree of retinal functional damage, and changes in sub-retinal fluid (SRF) and central macula thickness (CMT) on OCT. At 6 months, removal rate of leakage on Fluorescene Angiography (FA) and recurrence of the disease will be evaluated to compare the recurrence rate of study group and control group undergoing sham procedure.

The subjects in the study group who only meet the conditions of retreatment at 3 ~ 5 months after selective retina therapy (SRT) may receive SRT up to twice again.

The subjects in the control group those who have not recovered naturally but have persistent clinical symptoms at 3 months will undergo SRT. And the subjects in the control group who only meet the conditions of retreatment at 5 months after SRT at 2 months.

And the subjects in the control group, who have experienced complete disappearance of SRF at 3 months after Sham procedure, but SRF is observed again at 4 or 5 months, may receive SRT up to twice again.

These subjects will be categorized into a separate subgroup and the efficacy and safety of SRT will be evaluated every visit.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam-si, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea Seoul St.Mary's Hospital
  • Seoul, Korea, Republic of
    • Nune Eye Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea Yeouido St.Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female adult patients aged 19 or over and less than 55
2. Patients who have had clinical symptoms of central serous chorioretinopathy over 3 months.
3. Patients whose best corrected visual acuity (BCVA) is at least 20/200 based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart (BCVA based on the ETDRS chart will be converted into logMAR)
4. Patients with Sub-Retinal Fluid (SRF) that has been going into the fovea continuously
5. Patients with ≥1 ~ ≤ 3 active leakage sites in Fundus Fluorescein Angiography (FA)

6. Patients who are of child-bearing potential and have agreed to use a medically acceptable contraceptive method during the study period

   ☞Medically acceptable contraceptive method: Condom, oral contraceptive pills that have been continued for more than three months, contraceptive injection or implants or intrauterine contraceptive device

7. Patients who voluntarily agree to participate in this study, and are willing to and able to follow the protocol.

Exclusion Criteria:

1. Patients with other retinal diseases such as choroidal neovascularization, polypoidal choroidal vasculopathy.
2. Patients with the conditions that make laser therapy difficult such as cataract or vitreous cloudiness.
3. Patients who have atrophy (diameter: ≥1000㎛) in the retinal pigment epithelium including the fovea.
4. Patients who had undergone laser or photodynamic therapy for central serous chorioretinopathy prior to the study participation.
5. Patients who have received steroid treatment (periocular, subtenon, intraocular) within the last one year
6. Patients who have received intraocular injection of anti-Vascular Endothelial Growth Factor (anti-VEGF) agent within the last six months.
7. Patients who have undergone ophthalmological surgery such as intraocular surgery or vitrectomy within the last six months.
8. Patients who have taken medication for central serous chorioretinopathy such as acetazolamide, spironolactone, and kalidinogenase [within the last two months].
9. Patients who have a history of allergy to fluorescein used for FA and indocyanine green used for ICG angiography.
10. Female patients who are pregnant or breastfeeding.
11. Patients with systemic diseases such as Cushing's syndrome, inflammatory diseases, uncontrolled hypertension and diabetes, liver diseases, kidney diseases.
12. Patients who have pigment epithelial detachment that is directly related to the point of leakage with a diameter of more than 1000 μm.
13. Patients who are considered ineligible for this study according to the investigator's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Laser; Once the energy to be applied for the treatment is determined through the laser irradiation testing, conduct laser therapy after selecting "T" corresponding to treatment laser on GUI.; At irradiation, excluding the circle area with a 100 μm radius (200 μm diameter) from the center of the fovea, irradiate laser in the form of surrounding the leakage site with an interval of 0.5-1 spot diameter (fovea = 1 spot size). As for the test spots, the serial number needs to be given for each treatment spot with the order of irradiation, as described above.; If pigment epithelial detachment (PED) occurs at the leakage site, irradiate laser around the PED (excluding the circle area with a 100 μm radius (200 μm diameter) from the center), not to the leakage site.; Within 2 hours after therapy, perform tests for efficacy evaluation (color fundus photography and fluorescein angiography).	Device: R:GEN Selective Retina Therapy; Selective Retina Therapy (SRT) is the treatment method using innovative laser technology with the wavelength absorbed by melanosomes such as laser photocoagulation, but due to short pulse width (1.7 µs) with 100 Hz repetition rate, Retinal Pigment Epithelium (RPE) cells may be destroyed only through the generation of microbubble around melanosomes (photomechanical action), and no thermal damage of normal cells or tissues may occur in the surrounding tissues. SRT influences the RPE wound healing, including migration and proliferation of RPE cells, which treats CSC in the mechanism of recovering RPE. Once RPE is recovered, the sub-retinal fluid may be pumped out and retinal function again recovered. Moreover, previous studies showed that SRT may stimulate a moderate increase of activated metalloproteinase (MMP), leading to the improvement of Bruch's membrane's transport property.
Sham Comparator: Sham Laser procedure; Select "C" corresponding to Sham Therapy on GUI of the laser device, and then perform Sham therapy.During Sham therapy, for patient's blinding, both light from the slit lamp and sound from laser oscillation are same as laser irradiation, and no laser oscillation will occur for treatment.; Perform subsequent procedures in the same manner as the procedure of study group.	Device: R:GEN Selective Retina Therapy; Selective Retina Therapy (SRT) is the treatment method using innovative laser technology with the wavelength absorbed by melanosomes such as laser photocoagulation, but due to short pulse width (1.7 µs) with 100 Hz repetition rate, Retinal Pigment Epithelium (RPE) cells may be destroyed only through the generation of microbubble around melanosomes (photomechanical action), and no thermal damage of normal cells or tissues may occur in the surrounding tissues. SRT influences the RPE wound healing, including migration and proliferation of RPE cells, which treats CSC in the mechanism of recovering RPE. Once RPE is recovered, the sub-retinal fluid may be pumped out and retinal function again recovered. Moreover, previous studies showed that SRT may stimulate a moderate increase of activated metalloproteinase (MMP), leading to the improvement of Bruch's membrane's transport property.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sub-retinal Fluid (SRF) Removal Rate	The percentage of subjects (%) who show complete removal of Sub-retinal Fluid (SRF) on Optical Coherence Tomography (OCT) is compared between study group and control group.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of Best Corrected Visual Acuity	The improvement of Best Corrected Visual Acuity is evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is compared between study group and control group.	3, 6 months
Degree of Retinal Functional Damage	The degree of retinal functional damage is compared between study group and control group.	3, 6 months
Change in Sub-retinal Fluid (SRF)	The change in Sub-retinal Fluid (SRF) (μm, mm3) on Optical Coherence Tomography (OCT) is compared between study group and control group.	3, 6 months
Change in Central Macular Thickness	The change on Central Macular Thickness (CMT) (μm) based on Optical Coherence Tomography (OCT) results are compared between the study and control group.	3, 6 months
Removal Rate of Leakage	The percentage (%) of participants who show complete removal of leakage in Fluorescene Angiography (FA) results is compared between study group and control group.	6 months
Recurrence Rate	The percentage (%) of participants who show recurrence is compared between study group and control group	6 months

Collaborators and Investigators

• Sponsor: LUTRONIC Corporation
• Investigators: Principal Investigator: Oh Woong Kwon, PhD, Nune Eye Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2016
• Primary Completion (Actual): April 2, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Central Serous Chorioretinopathy
• Other Study ID Numbers: LTN-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No