Registry and Natural History Study to Evaluate Clinical Non-Central Geographic Atrophy (GA) Who are CarRIers of High-Risk GeneTic Variants Associated with Age-Related Macular Degeneration (CLARITY): Study Outline and Available Baseline Data

Abstract

Purpose : Protein coding variations in genes involved in the alternative complement pathway are strongly associated with risk of age-related macular degeneration (AMD). AMD natural history studies in these genetically defined high-risk subpopulations will provide substantial longitudinal data to increase the understanding of disease progression and genotype-phenotype associations and will support future interventional studies. Identifying carriers of high-risk variants and determining the rates of progression of AMD in these subpopulations may allow development pathways for genetically targeted therapeutics.

Methods : CLARITY will enroll up to 375 patients with non-central GA secondary to dry AMD. Eligible patients must be carriers of rare or common high-risk variants in complement factor H (CFH) and associated complotypes, have 20/50 or better visual acuity, and no exudative AMD in the study eye. Outcomes and measurements include changes in GA lesion size (based on fundus autofluorescence and optical coherence tomography), best corrected visual acuity (BCVA), low luminescence visual acuity (LLVA), microperimetry, binocular reading speed, and patient-reported outcomes-the National Eye Institute Vision Function Questionnaire, Functional Reading Independence Index and aqueous humor sampling for biomarker analysis. Other imaging includes color fundus photography, near infrared reflectance and fluorescein angiography. The study is being conducted in 26 centers in the United States.

Results : To date, 345 patients have been genetically screened for participation, with 161 meeting the genetic eligibility criteria and 35 completing baseline evaluations. Mean age of eligible patients is 77.8 years and 60% are female. Mean BCVA at 4 meters is 47.6 letters, with mean LLVA at 4 meters of 27.9 letters.

Conclusions : CLARITY will be the largest and most complete natural history study to date in subjects with dry AMD who are carriers of high-risk variants. CLARITY uses a precision medicine strategy which will help inform and optimize the design of future interventional trials to develop safe and effective targeted therapeutics. Updated results, including genetic and imaging data, will be presented.

This is a 2020 ARVO Annual Meeting abstract.