Photodynamic laser therapy with verteporfin versus Placebo for chronic central serous chorioretinopathy: the Paint RCT
Central Serous Chorioretinopathy (CSCR)
This is a multicentre, double masked, placebo controlled randomised trial comparing half dose photodynamic therapy (PDT) using verteporfin with placebo infusion plus laser in adults with chronic central serous chorioretinopathy. Arm 1: Photodynamic Therapy (PDT) Participants receive verteporfin at 3 mg/m² body surface area, reconstituted and infused intravenously over 10 minutes. Fifteen minutes after infusion starts, PDT laser is applied using a 689 nm non thermal diode laser, at 50 J/cm² fluence for 83 seconds via a contact PDT lens. The treatment area is determined using indocyanine green angiography (ICGA) and corresponds to areas of hypercyanescence associated with subretinal fluid on OCT. PDT is administered at baseline, with re treatment at 4 and/or 8 months if subfoveal SRF ≥50 microns persists or recurs. Rescue PDT is permitted for ≥10 ETDRS letter loss with persistent or recurrent SRF. Arm 2: Placebo (Dextrose infusion + laser) Participants receive 15 mL of 50 mg/mL (5%) dextrose solution infused intravenously over 10 minutes, matching verteporfin infusion timing and masking. Fifteen minutes after infusion starts, the same laser procedure is performed with identical parameters, but without verteporfin. Re treatment at 4 and/or 8 months follows the same criteria, and rescue PDT is allowed under identical conditions. Route and duration: All treatments are given by intravenous infusion followed by laser activation. Total participant involvement is 12 months. Randomisation: Participants are randomised 1:1 using a secure web based minimisation system (Sealed Envelope Ltd), stratified by site and baseline BCVA (<68 vs ≥68 ETDRS letters). Masking is maintained for participants, clinical assessors, and outcome evaluators.
1. Participants must be aged 18 years or above. 2. Must have visual impairment due to Central Serous Chorioretinopathy (CSCR) of more than 4 months duration. This is defined by the subfoveal presence of subretinal fluid (SRF) on Optical Coherence Tomography (OCT) with a vertical thickness of at least 50 microns, along with the characteristic appearance of CSCR on Fundus Fluorescein Angiography (FFA) and Indocyanine Green Angiography (ICGA). 3. The study eye must have a best recorded visual acuity (BRVA) score of less than 70 ETDRS letters (equivalent to 6/12 Snellen). 4. The study eye must have clear ocular media and adequate pupillary dilatation to permit photography. 5. Participants must be able to provide written informed consent. 6. Women of childbearing potential must have a negative pregnancy test and be willing to use effective contraception. Women who are post-menopausal for over 12 months or are surgically sterile are also eligible.
General Exclusions: 1. Known hypersensitivity to verteporfin, iodine, sodium iodide, fluorescein, or indocyanine green. 2. Diagnosis of porphyria or a history of severe hepatic impairment (Child-Pugh score >6). 3. Currently breastfeeding. 4. Severe or end-stage renal impairment, defined as an estimated glomerular filtration rate (eGFR) of less than 15. 5. Current use of other photosensitising medicinal products, such as tetracyclines, sulphonamides, phenothiazines, and thiazide diuretics. 6. Use of any oral medication for the specific purpose of treating CSCR (e.g., eplerenone, spironolactone, rifampicin) within the last 6 months. 7. Use of oral corticosteroids within the last 3 months. 8. Participation in another clinical trial involving an Investigational Medicinal Product (IMP) within the last 30 days. Exclusions Specific to the Study Eye: 1. Evidence of choroidal neovascularization as seen on FFA, ICGA, or OCT-A. 2. Presence of subfoveal retinal pigment epithelial atrophy. 3. Any previous treatment with photodynamic therapy (PDT). 4. Receipt of any anti-VEGF therapy or previous thermal or micropulse laser therapy for CSCR within the last 6 months. 5. Presence of any other ocular disease which could be a cause of retinal or subretinal fluid accumulation, such as diabetic retinopathy. 6. Myopia greater than -6 dioptres.