All patients past planned primary endpoint; decision by Sponsor to wind down open-label follow-up activities.

This is a Phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at two dose levels: 2.5 mg and 5 mg

Inclusion Criteria:

Wet AMD Cohort

1. Treatment naïve wet age-related macular degeneration involving the fovea.
2. A lesion area <30 mm2 (12 disc areas) of any lesion type.
3. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
4. Decrease in vision in the study eye determined by the investigator to be primarily the result of wAMD.

DME Cohort

1. Treatment naïve diabetic macular edema.
2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
4. Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.

RVO Cohort

1. Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment.
2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the study eye.
3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or equivalent).
4. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible.
5. Decrease in vision in the study eye determined by the investigator to be primarily the result of macular edema secondary to RVO.

General Inclusion Criteria

• Adults ≥ 21 years.

Exclusion Criteria:

Wet AMD Cohort:

1. Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye.
2. Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye.
3. Prior intravitreal anti-VEGF therapy in the study eye.

DME Cohort:

1. Initial diagnosis of DME of more than 6 months from screening in the study eye.
2. Hard exudates in the fovea.
3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.
4. Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye.
5. Fibrovascular proliferation or tractional retinal detachment in the posterior pole in the study eye. If traction is present outside the posterior pole, it should be considered not at risk of increasing and threatening the macula with the use of anti-VEGF injections, in the investigator's judgement.

RVO Cohort:

1. Initial diagnosis of RVO of more than 4 months from screening in the study eye.
2. Active retinal or iris neovascularization in the study eye.
3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.

For all phase 1b subjects:

1. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
2. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
3. Any history of uveitis in either eye.
4. Significant media opacities, including visually significant cataract, in the study eye that might interfere with visual acuity assessments, optical coherence tomography, fundus photography, or with examination of the eye for assessment of safety.
5. Prior vitrectomy surgery in the study eye.
6. Active retinal disease other than the conditions under investigation.
7. Active ocular or periocular infection or inflammation in either eye.