Intervention: Salicylhydroxamic Acid
Trial phase: Phase 3
SMILES: O=C(NO)c1ccccc1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 129
Group description: Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.
Eligibility criteria:
Inclusion Criteria:

Willingness to provide signed Informed Consent Form
Age ≥ 18 years
For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study
Ability and willingness to return for all scheduled visits and assessments

Ocular Inclusion Criterion (Study Eye):

Foveal center-involved macular edema secondary to CRVO
BCVA using ETDRS charts of 20/40 to 20/320 (Snellen equivalent)
Mean central subfield thickness ≥ 250 μm on two optical coherence tomography (OCT) measurements (at screening [confirmed by the central reading center] and Day 0 [confirmed by the evaluating physician])
Media clarity, pupillary dilation, and participant cooperation sufficient to obtain adequate fundus photographs

Exclusion Criteria:

History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0
History of any anti-vascular endothelial growth factor (VEGF) or treatment in the fellow eye within 3 months prior to Day 0
History of any systemic anti-VEGF or pro-VEGF treatment within 6 months prior to Day 0
History of allergy to fluorescein
History of allergy to ranibizumab injection or related molecule
Relevant systemic disease that may be associated with increased systemic VEGF levels (namely, all active malignancies); history of successfully treated malignancies is not an exclusion criterion.
Uncontrolled blood pressure
Pregnancy or lactation
Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g., chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers, indicated difficulty in long-term follow-up, and likelihood of survival of less than 1 year)
Participation in an investigational trial within 30 days prior to Day 0 that involved treatment with any drug (excluding vitamins and minerals) or device that has not received regulatory approval at time of study entry

Ocular Exclusion Criteria (Study Eye):

Prior episode of retinal vein occlusion (RVO)
Brisk afferent pupillary defect
History of radial optic neurotomy or sheathotomy
History or presence of age-related macular degeneration (AMD; dry or wet form)
History of any anti-VEGF treatment in the study eye within 3 months prior to Day 0
History of laser photocoagulation for macular edema within 4 months prior to Day 0
History of panretinal scatter photocoagulation or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 4 months following randomization
History of intraocular corticosteroid use within 3 months prior to Day 0
History of pars plana vitrectomy
History of intraocular surgery (including cataract extraction, scleral buckle, etc.) within 2 months prior to Day 0 or anticipated within the next 7 months following Day 0
History of yttrium-aluminum-garnet capsulotomy performed within 2 months prior to Day 0
Previous filtration surgery in the study eye
History of herpetic ocular infection
History of ocular toxoplasmosis
History of rhegmatogenous retinal detachment
History of idiopathic central serous chorioretinopathy
Evidence upon examination of vitreoretinal interface disease (e.g., vitreomacular traction, epiretinal membrane), either on clinical examination or OCT, thought to be contributing to macular edema
An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates
Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the study (e.g., uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass syndrome, or prior macula-off rhegmatogenous retinal detachment)
Visually significant hemorrhage obscuring the fovea and felt to be a major contributor to reduced visual acuity
Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., a 20/40 cataract)
Aphakia
Relevant ocular disease that may be associated with increased intraocular VEGF levels (namely, uveitis, neovascular glaucoma, neovascular AMD, diabetic retinopathy, diabetic maculopathy, or ocular ischemic syndrome)
Improvement of > 10 letters on best corrected visual acuity (BCVA) between screening and Day 0