Currently Enrolling Studies

PEDIG ATS-22

A Randomized Trial to Evaluate Sequential vs Simultaneous Spectacles plus Patching for Amblyopia in Children 3 to <13 Years Old

• Age 3 to <13 years at the time of randomization
• No previous treatment for amblyopia
• No previous spectacle or contact lens wear for more than a total of 24 hours
• Amblyopia associated with anisometropia, strabismus, or both
• Investigator is willing to prescribe spectacle wear followed sequentially by patching or simultaneous spectacles and patching treatment per protocol
• VA in the amblyopic eye approximately 20/40 to 20/200 (0.26 to 1.04 log MAR inclusive, 33 to 72 letters inclusive)
  • Age-normal VA in the fellow eye:
    •  3 years: approximately 20/50 or better, ≤ 0.44 log MAR, ≥ 63 letters
    •  4 years: approximately 20/40 or better, ≤ 0.34 log MAR, ≥ 68 letters 
    •  5-6 years: approximately 20/32 or better, ≤ 0.24 log MAR, ≥ 73 letters
    • 7-12 years: approximately 20/25 or better, ≤ 0.14 log MAR, ≥ 78 letters
• Interocular difference ≥ 3 log MAR lines (0.3 log MAR) or ≥ 15 letters
• No myopia greater than -6.00D spherical equivalent in either eye
• No planned strabismus surgery in the next 56 weeks
• No known allergy to adhesive patches or silicone

PEDIG X06

The primary objective of the study is to compare home versus office based visual acuity methods

• Age 3 to 17.5 years
• If the child wears contact lenses, the child must be able to perform all testing (in office and at home) in spectacle correction without contact lenses
• Have an iPhone 6 or a later version
• Be willing to return for a 3-month office visit
• Be able and willing to test VA at home 3 days after enrollment (Home test 1) and 1 day after home test 1 (Home test 2) and day before 3-month visit (Home Test 3)
• No use of atropine in the last 30 days, including the day of enrollment
• No use of atropine expected in the upcoming four months
• No dilation and cycloplegia within 48 hours of the first in-office VA measure

Protocol AM / DRCR

Randomized Trial Comparing Immediate versus Deferred Surgery for Symptomatic Epiretinal Membranes

• Age ≥50 years
• Vision better than 20/40
• Willing to wait for surgery
• No history of (DME), (RVO), or uveitis
• No retinal vascular disease, vitreous hemorrhage, retinal detachment, inflammatory disease, or associations other than vitreous syneresis, retinal break, or posterior vitreous detachment
• No known medical problems that will be a contraindication to surgery

Belvedere / Genentech / ML43000

A PHASE IV, MULTICENTER, OPEN-LABEL STUDY TO ASSESS CORNEAL ENDOTHELIAL CELLS IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH THE PORT DELIVERY SYSTEM WITH RANIBIZUMAB (PDS)

General Inclusion Criteria

• Age > 50 years, at the time of screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures

Study Eye Inclusion

• Initial diagnosis of nAMD < 18 months prior to screening
• Difference of < 10% in ECD at screening between the 2 eyes as measured by specular microscopy and determined by the independent reading center
• Availability of historical VA data and SD-OCT imaging prior to the first anti-VEGF IVT for nAMD
• Availability of comprehensive historical anti-VEGF injection data including anti-VEGF agent administered and date of administration from the first anti-VEGF treatment for nAMD
• Demonstrated response to at least two prior anti-VEGF intravitreal injections since diagnosis, as evidenced by the following:
  • Overall decrease in nAMD disease activity detected on screening SD-OCT as assessed by the investigator and confirmed by the central reading center
  • Stable or improved BCVA
• BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better
• All subtypes of nAMD lesions are permissible
• nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea)

Exclusion Criteria Study Eye

• Prior treatment with verteporfin for injection, external-beam radiation therapy, or transpupillary thermotherapy
• Previous treatment with corticosteroid intravitreal injection
• Previous laser (any type) used for AMD treatment
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of corneal transplant
• History of conjunctival surgery in the superotemporal quadrant

Exclusion Criteria Both Eyes

• Previous PDS implantation
• Previous intraocular surgery (including cataract surgery) within 6 months of study enrollment
• Prior vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
• Prior pars plana vitrectomy surgery
• Previous intraocular device implantation excluding intraocular lenses
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• Prior participation in a clinical trial involving any intravitreal anti-VEGF agents
• Intraocular laser therapy including selective laser trabeculoplasty, yttrium-aluminum garnet (YAG), prophylactic peripheral iridotomy within 1 year of screening, or YAG capsulotomy within 3 months of screening
• Contact lens wear in either eye within 2 months of screening
• Any prior ocular trauma (blunt or penetrating)
• History of corneal transplantation, including partial-thickness corneal grafts (e.g., Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty)
• Prior treatment with brolucizumab
• Prior treatment with any anti-VEGF biosimilar agents
• Prior treatment with faricimab within 2 months of screening
• Prior treatment with aflibercept 8 mg within 2 months of screening
• Prior treatment with external-beam radiation therapy or brachytherapy

Macular Neovascularization Lesion Characteristics

• Study Eye
  • Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 mm2) in size
  • Subfoveal fibrosis or subfoveal atrophy
• Either Eye
  • MNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
  • MNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)

Exclusionary Concurrent Ocular Conditions

• Study Eye
  • Retinal pigment epithelial tear
  • Retinal tears or peripheral retinal breaks on depressed fundus examination that are untreated, or treated within the 3 months prior to study enrollment
  • Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
  • Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus examination
  • Preoperative refractive error that exceeds 8 diopters of myopia, for patients who have undergone prior refractive or cataract surgery
  • Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia
  • Preoperative refractive error that exceeds 5 diopters of hyperopia, for patients who have undergone prior refractive or cataract surgery
  • Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure [IOP] > 25 mmHg or a cup-to-disc ratio > 0.8, despite treatment with antiglaucoma medication) and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient’s participation in the study
  • Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)
  • Conjunctival pathologies (e.g., pterygium, scarring, thinning, fibrosis) in the superotemporal quadrant
  • History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
  • Ectropion, entropion, or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure
  • Trichiasis
  • Corneal neuropathy
  • Lagophthalmos or incomplete blink
  • Active or history of facial nerve palsy/paresis
• Non-Study Eye
  • Concurrent PDS implantation
• Either Eye
  • Aphakia or absence of the posterior capsule
  • Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
  • Corneal ECD < 1500 cells/mm2 in either eye at screening as determined by the independent reading center
  • Fuchs endothelial corneal dystrophy Grade > 2
  • Previous corneal endothelial cell damage, including from blunt or surgical trauma (including complicated cataract surgery resulting in complicated lens placement such as anterior chamber intraocular lens, sulcus intraocular lens, or aphakia)
  • Any ocular condition that precludes obtaining an analyzable specular microscopy image
  • Active or history of corneal edema
  • Active or history of corneal dystrophies
  • Active or history of iridocorneal endothelial syndrome
  • Active or history of pseudoexfoliation syndrome
  • Active or history of herpetic keratitis or kerato-uveitis (including herpes simplex virus and herpes zoster virus)
  • Any active or history of uveitis (e.g., idiopathic, drug-associated or autoimmune-associated)
  • Active or history of keratitis, scleritis, or endophthalmitis
  • Active ocular or periocular infection (i.e., conjunctivitis, dacryocystitis)
  • Active or history of Sjogren’s syndrome or keratoconjunctivitis sicca
  • Active or history of floppy eyelid syndrome
  • Active or history of chronic eye rubbing
  • Active thyroid eye disease

Concurrent Systemic Conditions

• History of uncontrolled blood pressure (defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg, while a patient is at rest)
• Active or history of autoimmune diseases, such as rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner’s)
• History of stroke within the last 3 months prior to screening
• Uncontrolled atrial fibrillation within 3 months of screening
• History of myocardial infarction within the last 3 months prior to screening
• History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the implant and that might affect interpretation of the results of the study or renders the patient at high risk of treatment complications, in the opinion of the investigator
• Current active systemic infection
• Use of any systemic anti-VEGF agents
• Chronic use of oral corticosteroids (>10 mg/day of prednisone or equivalent)
• Active cancer within 12 months of enrollment except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months
• Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month prior to screening (excluding vitamins and minerals)
• Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the screening visit

Burgundy / Genentech / BP41670

A THREE-PART, PHASE I STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF ZIFIBANCIMIG FOLLOWING INTRAVITREAL ADMINISTRATION OF MULTIPLE ASCENDING DOSES AND CONTINUOUS DELIVERY FROM THE PORT DELIVERY IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (BURGUNDY)

General Inclusion Criteria

• Willing to allow AH collection
• Age > 50 years, at the time of signing the informed consent

Study Eye Inclusion

• CNV exclusively due to AMD and with the following characteristics:
  • Active CNV lesions must be subfoveal or juxtafoveal with a subfoveal component related to CNV activity (e.g., subretinal fluid, intraretinal fluid, retinal pigment epithelium (RPE) detachment, etc.) at the time of screening (as assessed by the central reading center).
  • All subtypes of CNV are permissible
• Diagnosis of nAMD within nine months prior to the screening visit
• Previous treatment with at least two IVT anti-VEGF or anti-VEGF/Ang-2 administrations for nAMD per SoC within six months prior to the screening visit. The last IVT administration must have occurred at least 21 days prior to the screening visit
  • If a participant did not receive at least two IVT anti-VEGF or anti-VEGF/Ang-2 administrations as described above but is otherwise eligible for the study, the participant can be treated in a run-in period to meet this specific criterion
• Demonstrated response to prior IVT anti-VEGF or anti-VEGF/Ang-2 treatment since diagnosis, as evidenced at screening by the following:
  • Previous decrease in nAMD disease activity detected on SD-OCT, as assessed by the Investigator and confirmed by the central reading center AND
  • Previously stabilized or improved BCVA (as assessed by the Investigator)
• Availability of historical VA data prior to the first anti-VEGF or anti-VEGF/Ang-2 treatment for nAMD until the time of study enrollment
• Decreased BCVA attributable primarily to nAMD with letter score of 78 to 34 letters (inclusive) on ETDRS-like charts at screening. In case both eyes of a participant are eligible, the study eye selection is at the Investigator’s discretion

Exclusion Criteria Study Eye

• History of vitrectomy surgery, submacular surgery, other intraocular surgery, or any planned surgical intervention during the study period
• Cataract surgery without complications within three months preceding the screening visit or planned during the study period. Cataract surgery with complications falls under Exclusion Criterion 1.
• Prior macular treatment with verteporfin, external beam radiation therapy, transpupillary thermotherapy, or any type of laser photocoagulation
• Subretinal hemorrhage > 50% of the total lesion area and/or involving the fovea
• Retinal pigment epithelial tear involving the macula
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of rhegmatogenous retinal tears or peripheral retinal breaks within three months prior to the screening visit
• Any concurrent intraocular conditions (e.g., cataract, diabetic retinopathy, epiretinal membrane with traction, macular hole) that, in the opinion of the Investigator, could either:
  • Require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition; or
  • Likely contribute to loss of BCVA over the study period if allowed to progress untreated; or
  • Preclude any visual improvement due to substantial structural damage
• Actual or history of myopia > -8 diopters
• Uncontrolled ocular hypertension or glaucoma (defined as IOP >25 mm Hg or a cup to disc ratio > 0.8, despite treatment with antiglaucoma medication) and any such condition the Investigator determines may require a glaucoma-filtering surgery during a participant’s participation in the study
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant
• Prior treatment with any medication for geographic atrophy.
• Prior treatment with any anti-VEGF-C or anti-VEGF-D inhibitors

Fellow Eye Exclusion

• BCVA letter score using ETDRS charts of < 34 letters
• Treatment with anti-VEGF or anti-VEGF/Ang-2 agents within one month prior to Day 1.

Either Eye Exclusion

• CNV due to causes other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, uveitis or central serous chorioretinopathy
• Active intraocular inflammation (grade trace or above), infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
• History of uveitis, including history of any intraocular inflammation following IVT anti-VEGF or anti-VEGF/Ang-2 injections
• Prior treatment with brolucizumab         
• Prior gene therapy for nAMD

Concurrent Systemic Conditions Exclusions

• Uncontrolled blood pressure ([BP] defined as systolic > 180 mm Hg and/or diastolic > 100 mm Hg while participant at rest), at screening
• Uncontrolled atrial fibrillation within three months of screening
• History of myocardial infarction within last 12 months prior to screening
• History of stroke within last 12 months prior to screening
• Chronic use of oral corticosteroids (> 10 mg/day of prednisone or equivalent).
• Current systemic treatment for a confirmed active systemic infection
• Bleeding disorders, including platelet disorders, acquired or hereditary coagulations disorders, and acquired or hereditary vascular disorders
• Active malignancy within 12 months of screening except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen (PSA) for > 12 months
• Any major illness or surgical procedure within one month prior to screening
• Any febrile illness within one week prior to screening or Day 1
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the IMP or placement of the PD implant that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the Investigator

Ascent / REGENXBIO

A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants with nAMD

• Age ≥ 50 years and ≤ 89 years
• BCVA of 20/32 to 20/160
• CNV lesion size < 10-disc areas (typical disc area = 2.54 mm2)
• Received 10-12 anti-VEGF injection 12 months prior to Screening Visit 1
• Study eye with nAMD diagnosed > 4 years
• Pseudo phakic-at least 12 weeks post cataract surgery
• No central 1mm Subfoveal fibrosis or atrophy
• No chemotherapy and/or radiation in the 5 years prior to Screening Visit
• No heart attack, Stroke or TIA 6 months prior

iStar MINIject / iStar Medical / MINIject SO Integrated System CS627

A Prospective, multicenter masked clinical trial to evaluate the safety and effectiveness of the MINIject CS627 implant in subjects with open angle glaucoma

Major Inclusions:

• Males and females, 46 years of age or older
• A diagnosis of POAG, who are candidates for medical therapy, laser treatment, or glaucoma-filtering surgery, with optic nerve pathology described by one or more of the following:
  • Diffuse thinning, focal narrowing, or notching of the optic disc rim, especially at the inferior or superior poles with or without disc hemorrhage; or
  • Localized abnormalities of the peripapillary retinal nerve fiber layer, especially at the inferior or superior poles; or
• Optic disc neural rim asymmetry of the two eyes consistent with loss of neural tissue
• A reliable Humphrey-Zeiss 24-2 SITA Standard or equivalent visual field for the study eye, defined as fixation losses, false positive, and false negative errors less than 33%
• Visual field defects consistent with glaucomatous optic nerve damage using Humphrey-Zeiss 24-2 SITA Standard or equivalent (conducted within 90 days of Screening is acceptable), with a mean deviation not worse than -12 dB; and at least one of the following two findings:
  • A cluster of 3 or more points in an expected location of the visual field depressed below the 5% level, at least 1 of which is        depressed below the 1% level on the pattern deviation (PD) plot;
  • Glaucoma hemi-field test “outside normal limits”.
• Pseudophakic with prior uncomplicated cataract surgery ≥ 12 months prior to enrollment and with posterior chamber IOL in capsular bag
• Medicated IOP of ≤ 25 mmHg, or unmedicated IOP of ≥ 21 mmHg and ≤ 33 mmHg at the Screening Visit

Major Exclusions:

• Any diagnosis of glaucoma other than POAG, including, angle closure, congenital, or secondary glaucoma (e.g., pseudoexfoliative, pigmentary, neovascular, uveitic, traumatic, steroid induced, lens induced, malignant or glaucoma associated with increased episcleral venous pressure)
• Grade 2 (narrow, 20 degrees), grade 1 (extremely narrow, less or equal to 10 degrees) and grade 0 (closed or slit) according to Shaffer Angle Grading System
• Use of more than 4 classes of ocular hypotensive medications including each class of ocular hypotensive medication in combination medications. Each IOP-lowering drug in a combination medication will be recorded, reported and counted separately.
• Inability to perform Humphrey Visual Field (HVF) or equivalent perimetric testing in either eye
• Subjects with potential for significant risk by a washout of medication, including the following:
  • Subjects with potential for significant risk by a washout of medication, including the following:
    • On PD plot, greater than or equal to 75% of points depressed below the 5% level and greater than or equal to 50% of points depressed below 1% level; or
    • At least 50% of points (i.e., 2 or more) within central 5 degrees with sensitivity of < 0 dB on the dB plot; or
    • Points within the central 5 degrees of fixation with sensitivity < 15 dB in both hemifields on the dB plot
  • Subjects with fixation-threatening glaucoma in either eye noted at the qualifying visit, i.e., visual field defects threatening fixation defined as any (1 or more) point(s) within the central 5° depressed below the 5th percentile on PD plot unless this/these points are >25 dB on Threshold Values (decibel) plot.
• History of elevated IOP due to steroid response in the designated study eye
• BCDVA worse than 20/80 in either eye

COAST SLT study/ University of Pittsburg Collaborative study

A 48 month randomized clinical trial to compare the efficacy and safety of standard versus low energy primary SLT in eyes with OHT, mild-moderate POAG, and to determine the optimal interval and energy for repeat SLT (as needed at initially assigned energy versus annually at low energy)

Major Inclusions:

• Age 18 years or older
• Each eye with BCVA at least 20/200
• Both eyes with a qualifying diagnosis:
  • Ocular hypertension: IOP > 21 mmHg without glaucomatous optic neuropathy,
  • Early primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation >-6.0 dB with no points in the central 5° 12 dB and no more than 1 central 5° point
  • Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation -6.0 dB to >-12 dB and no more than 1 central 5° point

Major Exclusions:

• Severe POAG, pigmentary glaucoma, narrow angle glaucoma and all other types other than POAG.
• Mean IOP > 35 mmHg in either eye at the Eligibility or Baseline visit
• Contraindications to SLT, brimonidine, or any other study intervention
• Any intraocular surgical procedure within the past 6 months in either eye
• Pregnancy or planning to become pregnant in next four years

EyeBio LTD, EYE-RES-102 

General Inclusion Criteria:

1. Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity
2. Be male or female ≥18 years of age
3. If female, have a negative serum pregnancy test at screening and further negative urine tests immediately before each dose of study medication if the participant is a female of childbearing potential (including those with <2 years since the onset of menopause, amenorrhea for <1 year, or not surgically sterile); such participants must agree to use a highly effective method of contraception for 30 days after the last dose of study drug (see Appendix B). She must also agree not to donate oocytes from the time of the first dose and for 30 days after the last dose of study drug 
4. If male, be surgically sterile for at least 12 weeks, or agree to use a highly effective method of contraception, such as a condom and a second highly effective method of contraception from screening up to and including 90 days after the last dose of study drug (see Appendix B). He must also agree not to donate sperm from the time of the first dose until 12 weeks after the last dose of study drug
5. Have type 1 or type 2 diabetes mellitus and a HbA1c of ≤12%
6. Have a BCVA ETDRS letter score between 75 and 24, inclusive, in the study eye at screening and on day 1. In the event both eyes are eligible, the worse-seeing eye should be enrolled in the trial
7. Have a decrease in vision in the study eye determined by the investigator to be primarily the result of DME
8. For participants who are treatment naïve for DME, the diagnosis must have been made within 9 months of screening. For all treatment-experienced participants, the first treatment should have been no longer than 3 years prior to the screening visit. If the participant has received anti-VEGF therapy previously, the last treatment must have been ≥90 days prior to the screening visit. For patients treated previously with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO), treatment must have been ≥120 days prior to the Screening visit
9. Have a CST of ≥325 μm in the study eye on SD-OCT as determined by the IRC at screening

General Exclusions

1. Be pregnant or breastfeeding
2. Have had renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis or have renal failure anticipated to require hemodialysis or peritoneal dialysis at any time during the study

3. Have uncontrolled blood pressure, defined as systolic ≥180 mmHg and/or diastolic ≥100 mmHg while a participant is at rest

   • If a participant’s initial reading exceeds these values, a second reading may be obtained later the same day or on another day during the screening period. If the participant’s blood pressure is controlled by antihypertensive medication, the participant should be taking the same medication continuously for at least 30 days prior to Day 1

4. Have history of stroke (cerebral vascular accident) or myocardial infarction within 180 days prior to Day 1
5. If treatment-experienced for DME have a history of any of the following treatments within the noted time windows:
   • Have had prior treatment with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO) within 120 days prior to the Screening visit in the study eye
   • Have had an IVT with other anti-VEGF treatments (ranibizumab, bevacizumab, aflibercept [2 mg], brolucizumab, pegaptanib sodium) in the study eye within 90 days of the Screening visit
   • Had prior IVT investigational agents in either eye at any time
   • Had treatment with ocriplasmin (JETREA®) in the study eye at any time
   • Had previous use of ILUVIEN® at any time, of OZURDEX® IVT implants within 180 days of the Screening visit, or any other intraocular or periocular corticosteroids in the study eye within 90 days of the Screening visit
6. Are currently using drugs with known retinal toxicity (e.g., Hydroxychloroquine, pentosan polysulfate sodium, and amiodarone)
7. Have history of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of screening
8. Have any treatment for complications of cataract surgery with steroids or yttrium-aluminum garnet (YAG) laser capsulotomy within 90 days of Screening
9. Have had pan-retinal photocoagulation or focal/grid thermal laser photocoagulation in the study eye within 90 days of screening
10. Have tractional retinal detachment in the study eye
11. Have advanced or uncontrolled glaucoma (defined as IOP ≥25 mmHg despite treatment with antiglaucoma medication) in the study eye
12. Have had glaucoma-filtering surgery (trabeculectomy or tube shunt) in the study eye
13. Have any history of retinal detachment or treatment or surgery for retinal detachment in the study eye
14. Have any history of uveitis in either eye
15. Have significant media opacities, including cataract, in the study eye that might interfere with VA, assessment of safety, OCT, or fundus photography in the opinion of the reading center
16. Have a cataract in the study eye that, in the judgment of the investigator is expected to require surgical extraction within 4 months of screening
17. Have aphakia in the study eye
18. Have an allergy to fluorescein dye
19. Have had vitrectomy in the study eye
20. Have known or former (if the participant has undergone refractive and/or cataract surgery) refractive error with a spherical equivalent of ≥±8 diopters
21. Have active retinal disease other than the condition (DME/diabetic retinopathy) under investigation in the study eye
22. Have any history or evidence of a concurrent ocular condition present in the study eye that, in the opinion of the investigator, could require either medical or surgical intervention or affect macular edema or alter VA during the study (e.g., Vitreomacular traction, epiretinal membrane, choriodal neovascularization due to NVAMD or other causes, such as pathological myopia, angioid streaks, presumed ocular histoplasmosis syndrome, and multifocal choroiditis)
23. Have active or suspected ocular or periocular infection or inflammation in either eye at day 1
24. Currently have evidence of, or a history of any clinically significant autoimmune, cardiovascular, hematologic, hepatic, metabolic, peripheral vascular, renal, or respiratory disease, which, in the opinion of the investigator, would prevent the participant from completing the required assessments for this study
25. Have a known hypersensitivity to any of the components of EYE103 formulation or prior hypersensitivity to mAbs
26. Have previously participated in any study of EYE103
27. Presence of amblyopia, amaurosis or ocular disorders with BCVA <35 letters (ETDRS testing charts) in the fellow eye at screening
28. Have macular edema in the study eye considered to be secondary to a cause other than DME (e.g., Retinal vein occlusion, Irvine-Gass syndrome)
29. Have active iris or angle neovascularization or neovascular glaucoma in the study eye
30. Have active proliferative diabetic retinopathy (PDR) in the study eye (e.g., Any vitreous or preretinal hemorrhage, active neovascularization at optic disc [NVD], or active neovascularization elsewhere [NVE] that in the opinion of the investigator would require treatment within 24 months)
31. Have structural damage to the center of the macula in the study eye that, in the opinion of the investigator or sponsor, is likely to preclude improvement in BCVA, including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia, organized hard exudates in the foveal center, or other evidence of chronic disruption of the macular architecture

Astellas 7317-CL-0003

Inclusion Criteria

General Inclusion Criteria

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] Authorization for US sites) must be obtained from the participant prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Participant is 50 years of age or older at the time of signing the informed consent form (ICF).
3. Participant must be willing to take tacrolimus and willing to discontinue any medications that have a known strong interaction with tacrolimus.
4. Participant is able and willing to undertake all scheduled visits and assessments up to the week 52 visit.
5. Participant who is taking an antidepressant must be on a stable and effective dosage and must be willing to take it reliably for as long as it is required.
6. Participant must be willing and medically suitable to undergo monitored anesthesia care during the vitrectomy and subretinal injection
7. Participant agrees to conform to local and institutional policies regarding active COVID-19 infections.
8. Participant agrees not to participate in another interventional study until the 52-week visit has been completed.
9. Female participant is not pregnant and at least one of the following conditions apply:
   • Not a woman of childbearing potential (WOCBP)
   • WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 52 weeks after investigational product (IP) administration.
10. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 52 weeks after IP administration.
11. Female participant must not donate ova starting at first dose of IP and throughout the study period and for 52 weeks after IP administration.
12. Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception  throughout the treatment period and for 52 weeks after IP administration.
13. Male participant must not donate sperm during the treatment period and for 52 weeks after IP administration.
14. Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 52 weeks after IP administration.

Ocular Inclusion Criteria 

Study Eye (Both Groups)

1. Participant has bilateral GA secondary to AMD. GA is defined as sharply demarcated areas of loss of the RPE.
2. Participant has no known history of CNV (wet AMD) in either eye prior to enrollment in the trial and no evidence of prior or active CNV with optical coherence tomography-angiography (OCT-A) or indocyanine green angiography (ICG-A), as assessed by the reading center.
3. Participant has absence of exudation as assessed by fluorescein angiography (FA) and spectral domain-optical coherence tomography (SD-OCT).
4. Participant has presence of either banded or diffuse hyper autofluorescence in the junctional zone of GA as assessed by the central reading center.
5. Participant has sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging.
6. Participant is pseudophakic.

Study Eye (Group 1 Only)

1. For Cohort 1, the participant has a BCVA between light perception and ≤ 23 ETDRS letters at the screening visit. For Cohorts 2 and 3, the participant has a BCVA score between 20 (≥ 20/400) and 37 (≤ 20/200) ETDRS letters at the screening visit.
2. Participant has the total GA area < 30.5 mm2 (< 12 disc areas [DA]).

Study Eye (Group 2 Only)

1. Participant has BCVA score between 38 (> 20/200) and 63 (≤ 20/63) ETDRS letters during the screening visit.
2. Participant has the total GA area of > 5.1 mm2 and < 17.8 mm2 (≥ 2 and ≤ 7 DA, respectively) and must reside completely within the FAF imaging field (Field 2 to 30 degree image centered on the fovea). If GA is multifocal, at least 1 focal lesion must be ≥ 2.5 mm2 (≥ 1 DA).
3. Participant has a difference in mean mesopic sensitivity ≤ 2 dB between 2 tests at screening. If not ≤ 2 dB, a third test may be conducted and mean values between the second and third assessments must be ≤ 2 dB.

Selection of the Study Eye

1. If the participant’s eligibility is confirmed and both eyes meet all ocular eligibility criteria, then the study eye will be the eye with the worst BCVA score at the screening visit; however, if the BCVA scores for the 2 eyes are within 10 letters (logMAR 0.2), then the eye with the larger GA will be selected as the study eye.

Exclusion Criteria

General Exclusions

1. Participant has a history of recurrent VZV infection or a clinical diagnosis of VZV infection within 4 weeks of the baseline visit or positive anti-VZV immunoglobulin M (IgM). Being positive for immunoglobulin G (IgG), indicative of a past infection (or vaccination), is not an exclusionary criterion.
2. Participant has a history of recurrent cytomegalovirus (CMV) infection or a clinical diagnosis of CMV infection within 4 weeks of the baseline visit or positive anti-CMV IgM. Being positive for IgG, indicative of a past infection, is not an exclusionary criterion
3. Participant has a positive tuberculosis (TB) test during the screening period by an interferon gamma release assay (e.g., QuantiFERON) within the 6 months prior to the screening. If a participant has tested negative for TB within the 6 months prior to the screening visit, retesting is not required unless clinically indicated
4. Participant has a history or suspected active infection of toxoplasmosis or presence of elevated immunoglobulin M (IgM) toxoplasmosis titer within 4 weeks of the baseline visit
5. Participant has an active infection (ocular or non-ocular) requiring the prolonged or chronic use of antimicrobial or anti-infective agents
6. Participant has a current malignancy or history of malignancy within the past 5 years*, except non-metastatic basal or squamous cell carcinoma or keratoacanthoma or Bowen’s disease or carcinoma-in-situ of the cervix that has been successfully treated
   • Participants with a history of malignancy that is cured or in remission > 5 years may be included if his/her treating physician (e.g., oncologist or hematologist) provides a written confirmation to support that the participant is fit to receive the study adjunct immunosuppressive medication
7. Participant has a history of a solid organ or bone marrow transplant
8. Participant has any condition that would prohibit the use of systemic immunosuppression with tacrolimus
9. Participant is receiving or has received any immunosuppressive therapy (IMT) (other than topical, inhaled or low-dose systemic corticosteroid use not exceeding 7.5 mg of prednisone daily [or equivalent]) within 6 weeks or 5 plasma half-lives, whichever is longer, prior to the administration of adjunct study medications
10. Participant has a history of myocardial infarction in previous 12 months and whose disease is either unstable and/or symptomatic (e.g., angina, dyspnea, etc.).

11. Participant has electrocardiogram (ECG) results that are clinically significant and could either jeopardize the safety of the participant, impact the participant’s ability to comply with study visit schedule or impact the validity of the study results. Participants with a mean Fridericia-corrected QT interval of > 430 ms (for males) and > 450 ms (for females) at screening must be cleared by a cardiologist prior to the baseline visit.

12. Participant has a study day diastolic blood pressure > 95 mmHg, at either the screening or baseline visit. Study day blood pressure is defined as the average of the second and third readings at a study visit. If the study day blood pressure exceeds the limits, 1 additional triplicate can be taken.
13. Participant has an estimated glomerular filtration rate (eGFR) of ≤ 45 mL/min, calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation
14. Participant has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyl transferase (GGT) and total bilirubin (TBL) ≥ 2 times the upper limit of normal (ULN).
15. Participant has severe anemia (hemoglobin < 9 g/dL [male] or hemoglobin < 8 g/dL [female]), leucopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet count < 80000/mm3) or polycythemia (hematocrit > 54% [male] or hematocrit > 49% [female])
16. Participant has a hemoglobin A1c > 8.5%.
17. Participant has a clinically significant coagulopathy (i.e., activated partial thromboplastin time [aPTT] ≥ 1.5 times the ULN and/or prothrombin time adjusted for the international normalized ratio [PT-INR] ≥ 2.0).
18. Participant has serology results indicative of having syphilis, Lyme disease, human immunodeficiency virus infection or active infection with HAV, HBV, HCV, or VZV.
19. Participant has a history of familial adenomatous polyposis or inflammatory bowel disease (i.e., Crohn’s disease, ulcerative colitis).
20. Participant has a history of allergic reaction to mydriatics or fluorescein.
21. Participant has a history of gene therapy or cell transplant therapy, including ASP7316, in a prior clinical study.
22. Participant has participated in any studies of an investigational drug (excluding vitamins and minerals for AMD studies) within 12 weeks prior to the screening visit.
23. Participant has participated with the study eye in any trial of a now FDA-approved complement inhibitor and/or has received an FDA approved complement inhibitor injection in the study eye within 24 weeks of the screening visit. After a washout period of 24 or more weeks, participants previously treated with a complement inhibitor will be eligible for participation, but participants will not be allowed to resume receiving any approved or investigational complement inhibitor in the study eye until the completion of the 52-week follow up period of the A7317-CL-0003 trial. Use of an FDA-approved complement inhibitor in the fellow, non-study eye is allowable.
24. Participant is unwilling to discontinue or avoid any CYP3A4 inducers (e.g., rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, St John's Wort) or participant is unwilling to discontinue or avoid protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir), direct Factor Xa inhibitors, direct thrombin inhibitors, verapamil, diltiazem or erythromycin while taking tacrolimus.
25. Participant has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, opiates, cocaine, phencyclidine and methadone), unless the drug is taken for a documented medical condition and under the supervision of a physician

Ocular Exclusions

Study Eye

1. Participant has macular degeneration due to causes other than AMD (e.g., Stargardt disease, cone rod dystrophy, toxic maculopathies, etc.)
2. Participant has developed CNV (wet AMD), also known as exudative AMD in either eye
3. Participant has foveal sparing as determined by the presence of potentially viable photoreceptors, as evidenced by presence of ellipsoid zone (EZ) ≤ 250 microns from the foveal center, based on reading center assessments at the screening visit.
4. Participant has a history of vitrectomy or submacular surgery, or any surgical intervention for AMD. Participants with a history of non-AMD-related surgical interventions (other than vitrectomy and submacular surgery) are potentially eligible if they meet all other inclusion/exclusion criteria
5. Participant has prior treatment with photodynamic therapy (e.g., Visudyne®), intraocular external-beam radiation therapy or transpupillary thermotherapy.
6. Participant has a history of previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion and proliferative diabetic retinopathy.
7. Participant has a history of intravitreal drug delivery (e.g., anti-VEGF drugs, intravitreal corticosteroid injection or device implantation) in either eye within 1 year prior to the screening visit for any condition other than AMD. Use of anti-VEGF injections at any point in time due to prior history of CNV (wet AMD) is not permitted as prior history of wet AMD is an exclusionary criterion. Note: A single intraoperative administration of a corticosteroid during cataract surgery for cystoid macular edema prophylaxis or a single administration of anti-angiogenic agent > 1 year prior to screening is permitted
8. Participant has an abnormality of vitreoretinal interface (e.g., tractional epiretinal membrane), which can interfere with measurement of macular thickness or with the potential for macular structural damage.
9. Participant has a history of cystoid macular edema, retinal vascular occlusion, central serous chorioretinopathy, macular hole or retinoschisis.
10. Participant has peripheral holes or other peripheral retinal lesions that are considered of rhegmatogenous potential (that is, with a risk of causing retinal detachment).
    • Note: A prior hole, tear or other retinal lesion of rhegmatogenous potential that was treated at least 3 months prior and no longer poses a risk is permitted, as is an atrophic hole that the investigator deems to be without rhegmatogenous potential

11. Participant has active or history of intraocular inflammation such as uveitis, chorioretinitis and optic neuropathy. (other than glaucoma).

12. Participant has presence of an ocular toxoplasmosis scar.
13. Participant has nevus of Ota (oculodermal melanocytosis), a pigmented choroidal lesion showing characteristics associated with high risk of malignancy (e.g., elevated lesion) or a choroidal nevus in the macula.
14. Participant has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or axial length > 28 mm at the screening visit, or myopic macular degeneration or posterior staphyloma.
15. Participant has glaucoma with uncontrolled IOP (defined as IOP > 25 mmHg despite treatment with anti-glaucoma medication) or is using more than 2 agents to control IOP or a history of glaucoma-filtering surgery.
16. Participant has a history of corneal transplantation
17. Participant has monocular vision; no light perception in the fellow eye or anophthalmic in the fellow eye.
18. Participant has a contraindication to pupil dilation
19. Participant has any other ocular condition that can interfere with the assessment of imaging data by the investigator’s discretion