This is a prospective, multicentre, sham-controlled, participant- and assessor-masked superiority trial with two parallel treatment arms which aims to investigate the safety and efficacy of subthreshold nanosecond laser (SNL) in a series of adults with sub-retinal fluid secondary to non-resolving central serous chorioretinopathy (CSCR) by visual and anatomical outcomes.

The study population will be individuals with adults (aged 18-70 years inclusive) with non-resolving CSCR (defined as CSCR present for a duration of more than 3 months presenting with either focal or diffuse leakage) who meet all eligibility criteria.

60 subjects total will be enrolled into the study - 40 randomized to receive SNL treatment and 20 to receive sham treatment as per a 2:1 randomization schedule and stratified by type of CSCR (focal vs diffuse).

The study has a 24-week study period with five scheduled visits: screening, randomisation (first treatment), 6-week follow up (with second treatment where eligible), 12-week follow-up , 18-week follow-up, and 24-week follow-up.

The primary outcome is the proportion of laser-treated study eyes that show resolution of sub-retinal fluid (SRF) as observed on optical coherence tomography (OCT) compared to sham-treated study eyes at 24 weeks.

The safety endpoint will be proportion of laser-treated eyes that lose ≥10 letters of of vision (measured on a standard vision chart) compared to sham-treated study eyes and fellow eyes over 24 weeks.

Inclusion Criteria:

1. Age 18-70 years
2. Both males and females
3. Individuals with non-resolving CSCR as defined by presence of any SRF on OCT for > 3 months from date of diagnosis to randomisation visit
4. BCVA of 35 to 80 letters (Snellen equivalent of 6/6 to 6/60) in the study eye
5. Ability, willingness and sufficient cognitive awareness to consent to the trial, received randomised SNL treatment or sham procedure, and complete all visits as per the study schedule

Exclusion Criteria:

1. A need for extraneous, continuous steroids to control any disease, including both systemic steroids (e.g., for systemic autoimmune conditions) and ocular steroids (e.g., for uveitis), or ongoing anabolic steroid use

2. Any systemic disease that leads to elevated endogenous steroid levels including raised 24h urinary cortisol level > 100 ug/24h consistent with Cushing's syndrome

3. Any ocular disease in the study eye, other than CSCR, which in the opinion of the investigator may significantly compromise assessment of the retina, or which would compromise the ability to assess any effect following SNL treatment including, but not limited to:

   • Age related macular degeneration
   • Any evidence of a neovascular membrane in the macular (either exudative or non-exudative)
   • Diabetic retinopathy (unless limited to fewer than 10 microaneurysms and/or small retinal haemorrhages, without retinal thickening on OCT)
   • Macular pathology or pigmentary abnormalities including but not limited to: pattern dystrophy, myopic maculopathy, angioid streaks, resumed ocular histoplasmosis syndrome, visually-significant epiretinal membranes, macular hole or pseudohole
   • Optic nerve pathology, including optic atrophy, history of optic neuropathy
   • Myopic crescent wider than 50% of the longest diameter of the optic disc, or closer than 1500 µm to the fovea
   • Retinal vascular diseases including branch or central vein or artery occlusion
   • Choroidal nevus within 2 DD of the fovea associated with depigmentation or overlying drusen, if these drusen are used to determine eligibility
   • Active uveitis or ocular inflammation
   • Corneal pathology precluding visualization of fundus or increasing the risk of using a contact lens, such as corneal dystrophy, recurrent corneal erosion syndrome or sensitivity to the application of a contact lens

4. History or presence of uncontrolled glaucoma or raised intraocular pressure which would preclude safe dilation of the pupil to allow adequate assessment and application of SNL treatment

5. History of prior laser surgery to the retina including subthreshold laser (focal retinopexy for a peripheral retinal tear performed more than 90 days prior to the entry into the study is permitted)

6. Significant cataract or other ocular media which, in the opinion of the investigator, significantly limits the visual acuity or view of the retina

7. Cataract surgery within three months preceding baseline, or a history of post-operative complications within the last 12 months preceding baseline in the study eye (uveitis, cyclitis, etc.)

8. Previous retinal or ocular surgery, the effects of which may now or in the future complicate assessment of CSCR (routine cataract surgery more than 3 months prior is permitted)

9. Known hypersensitivity to fluorescein

10. Use of any systemic or ocular medication known to be toxic to the retina, excluding tamoxifen unless there is evidence of toxicity

11. Pregnant or lactating women

12. Current participation in any other investigational ophthalmological clinical trial

13. Other health-related reasons which make an individual inappropriate for participation in this study based on the investigator's medical judgment