Gyrate Atrophy Ocular and Systemic Study

Inclusion Criteria:

• Participants must meet all the following inclusion criteria at the Screening Visitin order to be eligible to enroll into the genetic screening phase.

• Willing to participate in the study and able to communicate consent during theconsent process.

• Willing and able to complete all study visit assessments at each visit over theforty-eight (48) month study period. Age ≥ 12 years.

Must meet one (1) of the Genetic Screening Criteria below:

• At least 2 disease-causing variants in the OAT gene which are homozygous orheterozygous in trans, based on a report from a clinically certified lab, or areport from a research lab that has been pre-approved by the study GeneticsCommittee.

• At least 2 disease-causing variants in the OAT gene with unknown phase, based on areport from a clinically certified lab, or a report from a research lab that hasbeen pre-approved by the study Genetics Committee, AND must meet both of thefollowing phenotype criteria: .Classic fundus appearance of gyrate atrophy (based oninvestigator discretion) AND Elevated ornithine levels >300 μmol/L (documented onany prior lab report).

Note: if a participant has a variant(s) of unknown significance, they will still qualify if they meet the Genetic Screening Criteria above. Ocular Inclusion Criteria Participant must meet the following criteria at the Screening Visit to enroll into the genetic screening phase.

Both eyes must have a clinical diagnosis of retinal dystrophy. Both eyes must permit good quality photographic imaging (e.g., but not limited to, clear ocular media, adequate pupil dilation, stable fixation).

Exclusion Criteria:

• Participants must not meet any of the following exclusion criteria at the ScreeningVisit in order to be eligible to enroll into the genetic screening phase.

• Single pathogenic or likely pathogenic genetic variants known to be associated withautosomal dominant retinitis pigmentosa/retinal dystrophy (AD, heterozygous), X-374linked retinitis pigmentosa/retinal dystrophy (XL, hemizygous), or mitochondrialinheritance.

• Expected to enter experimental treatment trial at any time during this study.History of more than 1 year of cumulative treatment, at any time, with an agentassociated with pigmentary retinopathy, including hydroxychloroquine, chloroquine,thioridazine, and deferoxamine. Note: Since this is a Natural History Studycollecting data on the progression of Gyrate Atrophy, pregnant women will not bespecifically excluded from participation.

Ocular Exclusion Criteria:

• If either eye has any of the following ocular exclusion criteria at the ScreeningVisit, then the participant is not eligible to enroll into the genetic screeningphase.

• Current vitreous hemorrhage.

• Current or any history of tractional or rhegmatogenous retinal detachment.

• Current or any history of (for example, but not limited to prior to cataract orrefractive surgery) spherical equivalent of the refractive error worse than -8Diopters of myopia. • • • History of intraocular surgery (for example, but notlimited to cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) withinthe last 3 months.

• Current or any history of confirmed diagnosis of glaucoma (for example, but notlimited to glaucomatous VF changes or nerve changes, or history of glaucomafiltering surgery). e. Current or any history of retinal vascular occlusion orproliferative diabetic retinopathy.

• History or current evidence of ocular disease that, in the opinion of theinvestigator, may confound assessment of visual function.

• The following medications and treatments are prohibited as they can affectprogression of retinal pigmentosa. The participant must not have received orplanning to receive the following treatments.

• Any use of ocular stem cell or gene therapy.

• Any treatment with ocriplasmin.

• Treatment with Ozurdex (dexamethasone), Iluvien or Yutiq (fluocinolone 404acetonide) intravitreal implant.

The following medications and treatments are excluded within the specified timeframe:

• Treatment with an ophthalmic oligonucleotide within the last 9 months (lasttreatment date is less than 9 months prior to Screening Visit date).

• Treatment with any other product within five times the expected half-life of theproduct (time from last treatment date to Screening Visit date is at least 4115times the half-life of the given product).

• Treatment that can alter visual acuity between Screening and Baseline (e.g.,periorbital injections.)