Inclusion Criteria
At Screening Visit 1:

1. At least 50 years of age or older at Day 1.
2. Eligible to receive intraocular aflibercept therapy as per the FDA labels for the treatment of nAMD (Note: non-exudative CNV secondary to AMD is exclusionary)
3. Have adequate ocular media and adequate pupillary dilation in the study eye to permit good quality fundus imaging.
4. Treatment naïve juxtafoveal and/or subfoveal CNV secondary to nAMD with leakage involving the fovea prior to Screening, or have a diagnosis of nAMD in study eye within 4 months prior to or at screening and received 1 to 3 consecutive monthly (approximately every 4 weeks) anti-VEGF injections of any type (except Beovu®) with last injection approximately 4 weeks prior to Screening, with a CNV lesion of any type (i.e., predominantly classic, minimally classic, or occult [including polypoidal choroidal vasculopathy and retinal angiomatous proliferation]) that exhibits all of the following characteristics in the study eye at Screening as confirmed by CRC: (Note: For subjects who screen failed in the OTX-TKI-2023-AMD-301 study, or recently diagnosed with nAMD [within 4 months prior to screening], historical images could be used for eligibility assessment.)
   1. For treatment naïve or experienced study eye, A total lesion size (including blood, atrophy, fibrosis, and neovascularization) of ≤9-disc areas on fundus FA. Any macular hemorrhage should be resolved by Baseline (Day 1) prior to randomization, as assessed by the Investigator.
   2. For treatment naïve study eye, the CNV component area must be ≥50% of the total lesion size on FA
   3. For treatment naïve or experienced study eye, presence of active CNV confirmed on FA (evidence of leakage)
   4. For treatment naïve study eye, CNV exudation confirmed on SD-OCT (presence of intraretinal and/or subretinal fluid measured from ILM to RPE layer).
5. Have a BCVA ETDRS letter score of at least 34 or greater (approximately 20/200) in the study eye at Screening.
6. Have a CSFT ≤350 μm (measured from ILM to RPE layer) in the study eye at Week -12, confirmed by CRC.
7. Have a CSFT ≤ 350 μm (measured from ILM to RPE layer) in the study eye at Week -8 and < 35 μm increase from the lowest CSFT at any prior visits, confirmed by a CRC.
8. Are female who is postmenopausal for at least 12 months prior to Screening or surgically sterile; or male or female of childbearing potential willing to use two forms of adequate contraception from Screening until they exit the study.
9. Are able and willing to comply with all study requirements and visits.
10. Have provided written informed consent.

Exclusion Criteria

Individuals are not eligible for study participation if they meet any of the following criteria:

1. Presence of a disease other than CNV due to AMD in the study eye that could affect vision or safety assessments.
2. Monocular subject or BCVA score of <20 ETDRS letters or 20/400 in fellow eye at Screening.
3. Have evidence of a scar, fibrosis, or atrophy of >50% of the total lesion in the study eye.
4. Currently or previously treated with Syfovre® or Izervay™ for geographic atrophy in study eye. For fellow eye, treatment with Syfovre® or Izervay™ for geographic atrophy within 3 months prior to Screening.
5. Have previous laser photocoagulation or verteporfin photodynamic therapy (PDT) to the macula in the study eye.
6. Have history of intraocular surgery in the study eye including:
   1. cataract surgery or keratorefractive surgery (laser-assisted in-situ keratomileusis [LASIK], photorefractive keratectomy [PRK], etc.) or any anterior segment surgery within 3 months of Screening or
   2. have expectation of penetrating keratoplasty, vitrectomy, cataract surgery, or LASIK or any other intraocular surgery during the study period or
   3. have a history of vitreoretinal surgery (including vitrectomy) or other ocular surgeries including scleral buckle or glaucoma filtering/shunt surgery.
7. Have received gene therapy treatment or ranibizumab port delivery system (PDS, [Susvimo™]) for any reason in either eye.
8. Aphakia or sulcus intraocular lens in the study eye.
9. Have a history of significant ocular infection (bacterial, viral, or fungal) within the previous 3 months, or history of herpetic ocular diseases (including herpes simplex virus, varicella zoster, or cytomegalovirus retinitis) or toxoplasmosis gondii or chronic/recurrent inflammatory eye disease (i.e., scleritis, uveitis, corneal edema) in either eye.
10. Have evidence of a rhegmatogenous retinal detachment or visually significant/severe epiretinal membrane, vitreomacular traction syndrome, macular hole, tear of the retinal pigment epithelium in the macula, or other macular pathology deemed visually significant by the Investigator in the study eye.
11. Have a history of or presence of vitreous hemorrhage due to any other cause except posterior vitreous detachment in the study eye. Subject is still eligible if history of past hemorrhagic posterior vitreous detachment has resolved.
12. Have advanced glaucoma with uncontrolled IOP ≥25 mmHg despite IOP-lowering treatment in the study eye.
13. Have presence of other causes of CNV, e.g., pathologic myopia (spherical equivalent ≥ –8 diopters, or axial length of 26 mm or more), choroidal rupture, ocular histoplasmosis syndrome, or multifocal choroiditis in the study eye.
14. Have any current systemic or ocular treatment in the study eye with TKIs or systemic treatment with anti-VEGF agents.
15. Have ocular malignancy including choroidal melanoma in either eye.
16. Are receiving concurrent treatment with medications known to be toxic to the retina, lens, or optic nerve (e.g., chlorpromazine, phenothiazines, tamoxifen, hydroxychloroquine, pentosan polysulfate etc.).
17. Have a need for chronic therapy with systemic, intraocular or peri-ocular, or topical ocular corticosteroids in the study eye (>7 days) or have known allergy to fluorescein (e.g., bronchospasm, rash, etc.), or to any component of the study products.
18. Have symptomatic or unstable coronary artery disease, angina, congestive heart failure, or an arrhythmia requiring active procedural management (management with medications is permissible) within the last 30 days of the screening visit.
19. Have uncontrolled hypertension (defined as >160/100 mmHg, despite anti-hypertensive treatment).
20. Have a history of or presence of uncontrolled systemic disease or a debilitating disease (e.g., active malignancy within 2 years, Parkinson’s disease, dementia, liver failure, kidney failure requiring dialysis, progressive worsening of an inflammatory, autoimmune or pulmonary disease).
21. Had a myocardial infarction or other cardiovascular event (e.g., stroke) within the previous 6 months.
22. Have uncontrolled diabetes (defined as HbA1c >12%) despite treatment at Screening. Diabetic medication(s) could be adjusted if necessary and HbA1c should be repeated at Week -4 for eligibility assessment.
23. Are female and pregnant or breastfeeding or intend to become pregnant during the study.
24. Have participated in any study involving an investigational drug either in the US or outside the US within the past 30 days from Screening.
25. Are an employee of the site that is directly involved in the management, administration, or support of the study, or an immediate family member of the same.

Individual-Level Criteria
Inclusion

Individuals must meet all of the following inclusion criteria to be eligible to participate in the run-in phase of the study:

1. Age ≥ 50 years
2. Have the capacity to consent on his/her own behalf and follow instructions
3. Must understand English or Spanish
4. At least one eye that meets the study eye criteria listed below
5. Ability to cooperate with required visit procedures
6. Able to successfully and independently complete at least one self-scanning session on the Home OCT device located at the enrolling clinical site
7. Participant’s home has a table with a smooth, flat surface close to an electrical outlet to support placement of the Home OCT device for 2 years (device dimensions are 9.8” wide × 14.2” deep × 16.9” high)
8. Able to set up the Home OCT device by themselves or with assistance from others in their household (device is 16 pounds without packaging, 17.8 pounds with packaging)
9. Lives in an area with cell phone reception of 4G or above, or the location in which the Home OCT device will be placed has Wi-Fi connectivity (for the Home OCT data to be properly uploaded to the cloud)
10. Has a telephone number (home or cell) for Notal to call and provide Home OCT assistance and reminders
11. Participant is willing to perform once daily Home OCT monitoring tests for 2 years without significant interruption (such as travel of more than 14 days at a time)
12. Patients who spend part of the year in a different location will be permitted to enroll in the study if another DRCR clinical site is located near their second home, and they are willing to be seen at that location during follow-up. Additionally, their second home must meet the requirements for Home OCT device use specified above.

 Exclusion

1. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that may preclude successful completion of follow-up)
2. Known allergy or hypersensitivity to any component of the study drug or any drug used in the injection prep (including povidone iodine prep)
3. Participation in an investigational trial that involved treatment within 30 days of screening with any drug that has not received regulatory approval for the indication being studied.
   1. The participant should not receive or use any other drug or device in the study eye that is not FDA approved during the study.
4. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 2 years
   1. Women who are potential study participants should be questioned about the potential for pregnancy at baseline and prior to each injection. Women of childbearing potential will be required to have pregnancy testing or use an acceptable method of pregnancy prevention. Pregnancy test is required for all women of childbearing potential at screening. Investigator judgment is used to determine when a pregnancy test is needed during follow-up.
   2. Childbearing potential is defined as less than 12 months post-menopausal or not surgically sterile.
   3. Acceptable methods of pregnancy prevention are condom with spermicide, hormonal contraception, or IUDs.
5. Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next 2 years
6. Use of pentosan polysulfate, chloroquine, or hydroxychloroquine (Plaquenil®) within the last 5 years, or planned use during the next 2 years
7. Use, or plan to use, any at-home device related to monitoring nAMD not provided by the study, including ForeseeHome®, within the next 2 years
   1. Potential participants currently using ForeseeHome® may be enrolled if they 378 agree to stop use prior to randomization.

Study Eye Criteria
Inclusion

1. Best corrected E-ETDRS visual acuity ≥24 ETDRS letters (approximately 20/320 or better (Snellen))
2. Previously untreated, active MNV lesion (i.e., any intraretinal or subretinal fluid on OCT) secondary to age-related macular degeneration
3. MNV or sequelae of the MNV (i.e., pigment epithelium detachment, subretinal or sub-RPE hemorrhage, or subretinal, sub-RPE or intraretinal fluid) involving the foveal center
4. ≥ 1 intermediate drusen (>63 microns) in either eye OR late AMD (MNV or macular atrophy) in the contralateral eye

 Exclusion

1. History of rhegmatogenous retinal detachment, macular hole, or lamellar hole
2. History of vitrectomy
3. YAG capsulotomy performed within 1 month prior to the baseline visit.
4. History of trabeculectomy or Baerveldt or Ahmed tube for uncontrolled glaucoma
5. Minimally Invasive Glaucoma Surgery (MIGS) devices are allowed
6. History of retinal vein occlusion
7. Previous treatment for MNV (intravitreal injection of any anti-VEGF or anti-VEGF/anti-Ang2 agent, or any other AMD therapy)
8. Prior treatment with intravitreal injection of any anti-VEGF or anti-VEGF/anti-Ang2 agent or with macular laser for any indication
9. Treatment with intravitreal corticosteroids within the last 6 months
10. Current use of pegcetacoplan
11. Intraocular surgery (including cataract surgery) within 4 months prior to the baseline visit, or anticipated within the next 6 months
12. Active or recent (within 4 weeks) intraocular inflammation (grade trace or above)
13. Any condition that may preclude adequate imaging of the macula (e.g., dense cataract or other media opacity, severe ptosis)
14. The Notal Vision Monitoring Center must review the in-office Home OCT scan to confirm no pathology is affecting the quality of the image prior to randomization
15. Fibrosis or macular atrophy involving the foveal center
16. Epiretinal membrane distorting the foveal center
17. Significant vitreomacular traction in the foveal center
18. Aphakia
19. MNV due to other causes, such as ocular histoplasmosis, central serous retinopathy, or pathologic myopia
20. Retinal pigment epithelial tear involving the foveal center
21. Current vitreous hemorrhage
22. Polypoidal choroidal vasculopathy (PCV)
23. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis
24. High myopia; defined as 8 or more diopters of myopia or clinical evidence of high myopia
25. Uncontrolled glaucoma
26. Intraocular pressure must be<30 mmHg, with no more than one topical glaucoma medication, and no documented glaucomatous field loss for the eye to be eligible
27. Diabetic retinopathy worse than diabetic retinopathy severity level 35
28. Progressive retinal or other ocular diseases, such as amblyopia or ischemic optic neuropathy, which can affect visual acuity or are likely to affect visual acuity within the next 2 years
29. Any concurrent retinal vascular disease such as that, in the opinion of the investigator, could require medical or surgical intervention during the 2-year follow-up period

Inclusion Criteria
At Screening Visit 1:

1. Treatment naïve for nAMD in either eye at screening.
2. Have macular choroidal neovascularization due to nAMD who have had visual loss or would be expected to develop visual loss during the course of the study.
3. If foveal intraretinal and/or subretinal fluid is present on SD-OCT, it shall not exceed 500 µm (CSFT) as determined by Investigator.
4. Are eligible to receive intraocular aflibercept therapy for the treatment of nAMD.
5. Have a BCVA ETDRS letter score of at least 54 or greater (~ 20/80) in either eye.
6. Have adequate ocular media and adequate pupillary dilation in the study eye to permit good quality fundus imaging.
7. Are female who is postmenopausal for at least 12 months prior to screening or surgically sterile; or male or female of childbearing potential willing to use two forms of adequate contraception from screening until they exit the study.
8. Are able and willing to comply with all study requirements and visits.
9. Have provided written informed consent.

At Day 1:

10. Are older than 50 years of age at Day 1.
11. Have BCVA of at least 84 ETDRS letter score (~ 20/20 Snellen equivalent) at Day 1; OR have an increase of at least 10 ETDTS letters of BCVA from Screening (Visit 1) BCVA.
12. Have a CSFT of 350 µm or less in study eye at Day 1 as determined by Investigator.

Exclusion Criteria

1. Have presence of a disease other than CNVM due to AMD in the study eye that could affect vision or safety assessments.
2. Monocular subjects or a BCVA score of 20/200 in fellow eye at screening.
3. Have evidence of a scar, fibrosis, or atrophy of > 50% of the total lesion in the study eye.
4. Currently or previously treated Geographic Atrophy in study eye.
5. Have previous laser photocoagulation to the macula in the study eye.
6. Have history of intraocular surgery including cataract surgery or keratorefractive surgery (LASIK, PRK, etc.) or any anterior segment surgery in the study eye within 6 months of screening or have expectation of penetrating keratoplasty, vitrectomy, cataract surgery, or LASIK or any other intraocular surgery during the study period in the study eye or have a history of vitreoretinal surgery (including vitrectomy) or other ocular surgeries including scleral buckle or glaucoma filtering/shunt surgery in the study eye.
7. Have received gene therapy treatment or PDS in the fellow eye.
8. Have aphakia in the study eye.
9. Have a history of significant ocular infection (bacterial, viral, or fungal) within the previous 3 months, or history of herpetic ocular diseases (including herpes simplex virus, varicellazoster, or cytomegalovirus retinitis) or toxoplasmosis gondii or chronic/recurrent inflammatory eye disease (i.e., scleritis, uveitis, corneal edema).
10. Have evidence of a rhegmatogenous retinal detachment or visually significant/severe epiretinal membrane, macular hole, tear of the retinal pigment epithelium in the macula, or other macular pathology deemed significant by the Investigator in the study eye.
11. Have a history of or presence of vitreous hemorrhage in the study eye. Subject is still eligible if history of past hemorrhagic posterior vitreous detachment has resolved.
12. Have advanced glaucoma or uncontrolled IOP ≥ 25 mmHg despite treatment.
13. Have a history of receiving glaucoma filtration surgery in the study eye.
14. Have presence of other causes of CNV, e.g., pathologic myopia (spherical equivalent ≥ –8 diopters, or axial length of 26 mm or more), choroidal rupture, ocular histoplasmosis syndrome, or multifocal choroiditis in the study eye.
15. Have any current systemic or ocular treatment with TKIs or systemic treatment with antiVEGF agents.
16. Have an ocular malignancy including choroidal melanoma in either eye.
17. Are receiving concurrent treatment with medications known to be toxic to the retina, lens, or optic nerve (e.g., chlorpromazine, phenothiazines, tamoxifen, etc.).
18. Have a need for chronic therapy with systemic, intravitreal, or topical ocular corticosteroids or have known allergy to fluorescein (e.g., bronchospasm, rash, etc.), or to any component of the study products.
19. Have symptomatic or unstable coronary artery disease, angina, congestive heart failure, or an arrhythmia requiring active procedural management (management with medications is permissible) within the last 30 days of the injection of the implant.
20. Have uncontrolled hypertension (> 160/100 mmHg, despite medical treatment).
21. Have a history of or presence of uncontrolled systemic or debilitating disease.
22. Had a myocardial infarction or other cardiovascular event (e.g., stroke) within the previous 6 months.
23. Have uncontrolled diabetes as deemed by the Investigator.
24. Are female and pregnant or breastfeeding or intend to become pregnant during the study.
25. Have participated in any study involving an investigational drug either in the US or outside the US within the past 30 days.
26. Are an employee of the site that is directly involved in the management, administration, or support of the study, or an immediate family member of the same.