Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F

Prior treatment

• Current or any history of (e.g., prior to cataract or refractive surgery) spherical equivalent of the refractive error worse than -8 Diopters of myopia
• History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:
  • Any use of ocular stem cell or gene therapy
  • Any treatment with ocriplasmin
  • Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)
  • Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Screening Visit date is at least 5 times the half-life of the given product)
  • Treatment with Ozurdex (dexamethasone), Iluvien or Yutiq (fluocinolone acetonide) intravitreal implant

Other illness

• History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy (including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine)
  • Note: Pregnant women are not being specifically excluded from participation.
  • Ocular Exclusion Criteria
  • If either eye has any of the following at the Screening Visit, the participant is not eligible to enroll into the genetic screening phase.
• Current vitreous hemorrhage
• Current or any history of tractional or rhegmatogenous retinal detachment
• History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months
• Current or any history of confirmed diagnosis of glaucoma (e.g., based on glaucomatous VF changes or nerve changes, or history of glaucoma filtering surgery)
• Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
• History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function

Other

• Participants must not meet any of the following exclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
• Mutations in genes that cause autosomal dominant retinitis pigmentosa (ADRP), X-linked retinitis pigmentosa (RP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PCDH15
• Expected to enter experimental treatment trial at any time during this study

• Participants must meet all the following inclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
• Willing to participate in the study and able to communicate consent during the consent process
• Ability to return for all study visits over 48 months
• Age ≥ 8 years
• Not planning to enroll in an experimental clinical trial for the treatment of PCDH15 for the duration of this study
• Must meet one of the Genetic Screening Criteria, defined below:
  • Screening Group A: At least 2 disease-causing variants in the PCDH15 gene which are homozygous or heterozygous in trans, based on a report from a clinically certified lab (or a report from a research lab that has been pre- approved by the Genetics Committee)
  • Screening Group B: Only 1 disease-causing variant in the PCDH15 gene, based on a report from a clinically certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee)
  • Screening Group C: At least 2 disease-causing variants in the PCDH15 gene which are unknown phase, based on a report from a clinically certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee)
  • Note pertaining to all Screening Groups: if a participant has a variant(s) of unknown significance, he/she would still qualify if there is at least 1 disease-causing variant(s) on the PCDH15 gene. The Genetics Committee will review unique cases where segregation analysis is not feasible to determine eligibility.
  • Ocular Inclusion Criteria
  • Both eyes must meet all the following at the Screening Visit for a participant to be eligible to enroll into the genetic screening phase.
• Clinical diagnosis of retinal dystrophy
• Clear ocular media and adequate pupil dilation to permit good quality photographic imaging