Anti-VEGF Versus Prompt Laser or Observation for Proliferative Sickle Cell Retinopathy (ALPS)

• Signed Informed Consent Form
• Ability to comply with the study protocol
• Ability and willingness to undertake all scheduled visits and assessments
• Age 18 years at the time of providing informed consent
• Sickle cell hemoglobinopathy with active seafans with or without prior laser treatment
• Visual acuity > 20/40 / > 70 letters on ETDRS chart) for stage 3
• Visual acuity of 20/40 or worse (\< 58 letters) for stage 4 PSR and no known prior retinal disease that could explain the visual acuity impairment aside from PSR with vitreous hemorrhage.
• Ocular inclusion criteria for study eye:
• Patients who are IVT treatment-naïve in the study eye (i.e., have not received previous treatment with any anti-VEGF IVT or any corticosteroids periocular or IVT in the study eye)
• Sickle cell hemoglobinopathy with active seafans or vitreous hemorrhage as determined by indirect ophthalmic examination at screening.
• ETDRS visual acuity of > 70 letters ( > 20/40) at the baseline visit (Day 1) for stage 3 and \< 70 letters (20/70 or worse) for stage 4.(see Appendix 7)
• Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis

Exclusion Criteria:

• Any patient who has undergone major surgery within the past 3 months
• Diabetes mellitus with evidence of diabetic retinopathy
• Any known hypersensitivity to any of the components in the faricimab injection
• Any known hypersensitivity to any contrast media (e.g., fluorescein), dilating eye drops, disinfectants (e.g., iodine), or any of the anesthetics and antimicrobial preparations used by the patient during the study
• History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, or historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the investigator
• Active cancer within the past 12 months prior to Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer
• Stroke (cerebral vascular accident) or myocardial infarction within 12 months prior to Day 1
• Any febrile illness within 1 week prior to Day 1
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab
• Women of childbearing potential must have a negative urine pregnancy test result within 28 days prior to initiation of faricimab and a negative urine pregnancy test at the baseline visit (Day 1).
• Uncontrolled blood pressure, defined as systolic more than 180 mmHg and/or diastolic more than 100 mmHg (while patient is at rest in a sitting position); if a patient's initial reading exceeds these values, a second reading may be taken more or equal than 30 minutes later on the same day
• Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
• Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins or minerals) within 3 months (or 5 half-lives, whichever is longer) prior to Day 1, or during the course of this study
• Substance abuse occurring within 12 months prior to screening, in the investigator's judgment
• Use of systemic immunomodulatory treatments (e.g., IL 6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Use of any systemic corticosteroids within 1 month prior to Day 1
• Systemic treatment for suspected or active systemic infection Note: Ongoing use of prophylactic antibiotic therapy is acceptable
• Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Use of systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, or ethambutol) during the 6 months (or 5 half-lives, whichever is longer) prior to Day 1
• Receiving any treatment that leads to immunosuppression within 6 months (or 5 half-lives, whichever is longer) prior to Day 1
• Requiring continuous use of any medications or treatments listed as prohibited therapy
• Ocular exclusion criteria for study eye:
• Traction or rhegmatogenous retinal detachment
• Other retinovascular conditions such as diabetic retinopathy, retinal vascular occlusion (RAO, RVO)
• Uncontrolled glaucoma
• Media opacities precluding fundus photography
• Any history of or ongoing rubeosis iridis
• Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye prior to Day 1
• Any treatment for dry eye disease in the last month prior to Day 1 (e.g., cyclosporine eye drops, lifitegrast eye drops). Lubricating eye drops and ointments are permitted.
• Any intraocular surgery (e.g., cataract surgery) within 3 months prior to Day 1 or any planned surgery during the study
• Any glaucoma surgery prior to the screening visit
• History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy
• Uncontrolled glaucoma (e.g., progressive loss of visual fields or defined as intraocular pressure (IOP) ³25 mmHg at the screening visit despite treatment with anti-glaucoma medication)
• Any active or suspected ocular or periocular infections on Day 1 (i.e., any active infectious or noninfectious conjunctivitis, keratitis, scleritis, or endophthalmitis)
• Any presence of active intraocular inflammation on Day 1 (i.e., Standardization of Uveitis Nomenclature [SUN] criteria >0 or National Eye Institute [NEI] vitreous haze grading >0) or any history of intraocular inflammation
• Ocular exclusion criteria for non-study eye:
• Non-functioning non-study eye, defined as either:
• BCVA of hand motion or worse
• No physical presence of non-study eye (i.e., monocular)
• Legally blind in the patient's relevant jurisdiction