The goal of this Phase 2 clinical trial is to learn about ONL1204 Ophthalmic Solution in terms of safety and how well the drug works in patients that have a macula-off (central point of vision) rhegmatogenous retinal detachment (RRD). The main questions it aims to answer are:

• Does ONL1204 improve vision in macula-off RRD patients when used before retinal detachment repair surgery compared to patients that have surgery alone?
• Is ONL1204 safe to use as an add-on drug before retinal repair surgery?

Researchers will observe patients that receive two different dosages of ONL1204 Ophthalmic Solution (50 µg or 200 µg) compared to current standard therapy (no treatment) to see if there are differences in vision and safety outcomes.

Inclusion Criteria:

1. Adult subject, ≥18 years old at the time of informed consent
2. Able and willing to give informed consent and comply with all study visits and procedures
3. Presentation with macula-off RRD with a duration ≥24 hours up to 14 days from time of central visual decline to the Baseline (Visit 2) visit, inclusive (based on subject reported date of loss of central vision) in the Study Eye (SE)
4. Visual acuity with subject's current corrective lenses or pinhole of 20/100 (line scoring) on the Snellen or ETDRS chart to light perception (LP) in the SE
5. Visual acuity with subject's current corrective lenses or pinhole of 20/200 (line scoring) or better in the fellow eye
6. Determination by Investigator of macula-off status by clinical examination with confirmation by SD-OCT or B-scan ultrasound, if available.
7. SOC retinal reattachment surgery by means of a pars plana vitrectomy (with or without scleral buckle) is indicated
8. In the opinion of the Investigator, can safely undergo the IVT injection procedure at Baseline (Visit 2)
9. Surgical repair scheduled or anticipated to take place >12 hours after IVT injection or sham (Visit 2) and ≤10 days from Screening (Visit 1)

Exclusion Criteria:

1. Presence of a complex retinal detachment (RD) in the SE, identified by one or more of the following:

   1. Giant retinal tear, defined as retinal break ≥3 clock hours in extent
   2. Proliferative vitreoretinopathy grade C1 or worse on the Retina Society Terminology Committee Classification System
   3. Presence of tractional detachments as seen in proliferative retinopathies
   4. RRD in the setting of open- or closed-globe trauma
   5. RRD following endophthalmitis or infectious retinitis
   6. Similarly complex RD as determined by the Investigator

2. Use of silicone oil tamponade in the primary RD repair without planned removal by end of study

3. Vitreous hemorrhage or cataract in the SE that prohibits adequate examination for other exclusion criteria, per Investigator's discretion

4. Presence of ocular or periocular infection or intraocular inflammation in either eye

5. Uncontrolled glaucoma, as defined by an IOP >36 mmHg in either eye, at Screening

6. Any other significant ocular disease in the SE that, in the opinion of the Investigator, would preclude a postoperative (post-op) visual acuity of at least 20/30

7. History of previous ocular surgery in the SE for RD (excluding only barrier laser), endophthalmitis, glaucoma tube shunts, trabeculectomy, or ocular trauma

8. Any systemic condition or ocular condition in either eye that, in the opinion of the Investigator, makes the subject unsuitable for treatment with an investigational agent or that would compromise the safety and tolerability of assessments in the trial

9. History of and/or active:

   1. Autoimmune disease in active flare (i.e., not well controlled on current medications) with ocular involvement that, in the opinion of the Investigator, would impact ability to participate in the trial and/or alter the outcome of retinal reattachment surgery
   2. Ocular malignancy
   3. Proliferative diabetic retinopathy or diabetic macular edema or uveitis

10. Currently participating in other clinical trials or use of any other investigational drugs or devices within 12 weeks prior to Visit 1

11. Females who are pregnant or lactating, and women of childbearing potential (WOCBP) or men with female partners of childbearing potential who are not using at least one adequate contraceptive precaution (e.g., intrauterine device, oral contraceptive, barrier method, or other contraception deemed adequate by the Investigator)