Overview

Background

Age-related macular degeneration is a common eye disease in people over 50. The "dry" form of the disease can worsen into geographic atrophy, causing blind spots. Researchers want to learn if replacing older eye cells with younger ones can help treat this disease.

Objective

To test the safety of putting cells inside the eye as a possible future treatment for dry age-related macular degeneration.

Eligibility

People ages 55 and older who have geographic atrophy with loss of vision. People who have had "wet" macular degeneration in study eye are NOT eligible.

Design

Participants will be screened with:

• Medical history
• Physical exam
• Blood and urine tests
• Eye exam
• Eye photos
• Fluorescein angiography. An intravenous (IV) line is placed in an arm vein. A dye is injected. A camera takes pictures of the dye as it flows through the eyes' blood vessels.
• Electroretinography. An electrode is taped to participants' forehead. They sit in the dark. After 30 minutes, numbing eye drops and contact lenses are placed in their eyes. They watch flashing lights.
• Tuberculosis test
• Chest X-ray
• Electrocardiography. Sticky pads are placed on participants' chest to record the heart's electrical activity.

Participants will have at least 14 study visits over 5 and a half years. They will repeat screening tests.

Participants will have retinal pigment epithelium (RPE) transplantation surgery in one eye. For this, cells from participants' blood are turned into RPE cells. These cells are placed in their eye through a cut in their retina. They will get dilating eye drops, an IV line, and anesthesia that may make them sleep. A gas bubble will be put in their eye to help it heal. Participants will receive immunosuppressive medications to avoid transplant rejection.

Participants will be contacted yearly for up to 15 years.

Eligibility

• INCLUSION CRITERIA:

Participant Eligibility Criteria:

To be eligible, the following inclusion criteria must be met, where applicable.

• Participant must be 55 years of age or older.
• Participant must have a diagnosis of dry AMD, defined as presence (or history, as documented in available color fundus photographs) of at least one medium or large druse (greater than or equal to 63 micrometer diameter) in the macula in at least one eye; AND presence of GA in at least one eye.
• Participant must understand and sign the protocol s informed consent document.
• Any participant of childbearing potential must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing prior to RPE transplantation.
• Any participant of childbearing potential and any participant able to father children who has a partner of childbearing potential must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or must agree to practice an effective method of contraception through Month 12 in the study. Acceptable methods of contraception include:
  • Hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
  • Intrauterine device,
  • Barrier methods (diaphragm, condom) with spermicide, or
  • Surgical sterilization (tubal ligation).
• Participant must be medically able to comply with the study treatment (including

  ability to safely receive anesthesia for surgery), study testing and procedures, and follow-up visits.

Study Eye/Fellow Eye Eligibility Criteria

        The participant must have at least one eye meeting all inclusion criteria and none of the
        exclusion criteria listed below. The fellow eye must also meet the relevant eligibility
        criteria listed below.
        Study Eye Inclusion Criteria:
          -  The study eye must have one or more regions of geographic atrophy with total area of 1
             disc area or more. A region of geographic atrophy is defined as an area of uniform
             hypofluorescence on fundus autofluorescence (FAF) imaging, with greatest linear
             dimension at least 500 micrometer, with a border within 500 micrometer of the foveal
             center, not compatible with pigmentary changes, drusen, RPE detachment, drusenoid RPE
             detachment, hemorrhage, or other lesion. (Note: If macular geographic atrophy is
             contiguous with peripapillary atrophy, complicating calculation of total area, only
             atrophy temporal to a vertical line placed a half disc diameter temporal to the
             temporal border of the disc will be included in the total area of geographic atrophy
             calculated for eligibility purposes.)
          -  For participants in the first cohort, the study eye must have an ETDRS best-corrected
             visual acuity (BCVA) letter score of <= 53 and >= CF (i.e., Snellen equivalent between
             20/100 and CF), and the fellow eye must have a letter score no more than five letters
             worse than the study eye using Electronic Visual Acuity (EVA) testing. If the study
             eye is CF vision, then the fellow eye must be both (1) CF or better vision and (2)
             subjectively as good or better than the study eye according to the subject s
             perception. (Note: Letter scores within five or fewer letters of each other are
             accordingly considered equal for eligibility determination, and other factors may be
             used to select the study eye if both are eligible by BCVA.
          -  For participants in the second cohort, the study eye must have an ETDRS best-corrected
             visual acuity (BCVA) letter score of <= 58 and >= CF (i.e., Snellen equivalent between
             20/80 and CF), and the fellow eye must have a letter score no more than five letters
             worse than the study eye using Electronic Visual Acuity (EVA) testing. If the study
             eye is CF vision, then the fellow eye must be both (1) CF or better vision and (2)
             subjectively as good or better than the study eye according to the subject s
             perception. (Note: Letter scores within five or fewer letters of each other are
             accordingly considered equal for eligibility determination, and other factors may be
             used to select the study eye if both are eligible by BCVA.
          -  The compromise in visual acuity for the study eye must be judged predominantly
             secondary to dry AMD, in the judgment of the investigator.
          -  The study eye must have clarity of ocular media and degree of pupil dilation
             sufficient to permit adequate fundus photography and safe vitrectomy surgery.
          -  The study eye must be either pseudophakic or aphakic.
        EXCLUSION CRITERIA:
        A participant is not eligible if any of the following exclusion criteria are present:
          -  Participant is actively receiving another study medication / investigational product
             (IP).
          -  Participant has any condition that significantly increases risk of systemic
             corticosteroids or systemic steroid-sparing immuno-modulatory agents, such as
             uncontrolled diabetes mellitus, chronic hepatitis or liver failure, chronic renal
             failure, or present infection with HIV, syphilis, tuberculosis, hepatitis B, or
             hepatitis C (past infection now resolved, where applicable, is not exclusionary; but
             persistent infection, even if latent, is exclusionary).
          -  Participant has diagnosis of a malignancy expected to affect two-year survival.
          -  Participant is pregnant, breast-feeding, or planning to become pregnant through the
             first 12 months of the study.
          -  Participant has a family history of a retinal degeneration other than AMD suspected to
             play a role in the ocular phenotype of the participant in the judgment of the
             investigator, based on disease features and mode of inheritance, such as in a case of
             autosomal dominant retinal degeneration in a parent or child.
          -  Participant is taking, or has taken within the previous year, medication with known
             potential toxicity to the retina, optic nerve, or lens (such as chloroquine,
             hydroxychloroquine, ethambutol).
          -  Participant is taking any form of systemic anticoagulation which cannot be stopped for
             an indefinite period of time without significant risk. The determination of
             significant risk to the participant must be at the discretion of the study
             investigators and prescribing physician (or qualified alternative).
          -  Participant is unable or unwilling to give informed consent that includes use of
             medical records and clinical samples for current and future research.
        Study Eye Exclusion Criteria:
          -  The study eye has macular, subretinal or choroidal neovascularization, as assessed by
             FA and OCT; or any history of such neovascularization (as assessed by past available
             records or images).
          -  The study eye has serous or hemorrhagic pigment epithelial detachment, as assessed by
             FA and OCT, that is clinically significant in the judgment of the investigator.
          -  The study eye has a history of photodynamic therapy (PDT) or macular thermal laser
             photocoagulation, or history of intravitreal injection of anti-vascular endothelial
             growth factor (VEGF) agents or corticosteroids (excepting medications used
             peri-operatively at prior cataract surgery). The study eye has had intravitreal
             injections (anti-complement therapy) for treatment of dry AMD in the previous 12 weeks
             before enrollment. Any intravitreal injections with anti-complement therapy prior to
             12 weeks are not exclusionary.
          -  The study eye has an axial length > 25.0 mm.
          -  The study eye has had surgery in the previous 12 weeks, or laser capsulotomy in the
             previous four weeks.
          -  The study eye has chronic glaucoma; OR significant ocular hypertension, defined as
             documented intraocular pressure of >= 26 mmHg on at least two occasions in the absence
             of self-limited acute glaucoma; OR history of probable or definite steroid response
             manifesting as acute glaucoma or ocular hypertension, even if self-limited and no
             longer present; and the fellow eye has evidence for present or past glaucoma or ocular
             hypertension judged to significantly impact the risk of glaucoma in the study eye
             (including history of probable or definite steroid response). (Note: History of
             self-limited acute glaucoma in a study or fellow eye, if not secondary to steroid
             response, and if now resolved and not expected to recur (e.g., history of elevated
             intraocular pressure from retained visco-elastic after cataract surgery), is not
             exclusionary. History of glaucoma or ocular hypertension in the fellow eye, if not
             felt to significantly impact risk of glaucoma in the study eye, is not exclusionary.)
          -  The study eye has a condition materially increasing the risks of surgery or
             potentially affecting visual function over the next two years in the judgment of the
             investigator, such as chronic uveitis, diabetic retinopathy, keratitis, scleritis,
             optic neuropathy, untreated retinal detachment, macular edema from prior vein
             occlusion or other cause, proliferative vitreoretinopathy (PVR), vitreous hemorrhage,
             pathologic myopia, etc. A history of such conditions is not exclusionary, if judged to
             not materially increase risks of surgery or to potentially affect vision in the next
             two years in the opinion of the investigator.