This monocentric prospective longitudinal observational study will validate fundus-tracked dark adaptometry as an endpoint for future treatment trials in early and intermediate age-related macular degeneration (AMD). The study will characterize normative cone- and rod-mediated dark adaptation parameters in healthy volunteers, assess test-retest reliability, quantify sensitivity to change over time, evaluate diagnostic and prognostic validity against AMD stage and structural progression, and investigate imaging-, biomarker-, and genetics-based determinants of impaired dark adaptation.

Age-related macular degeneration (AMD) is a major cause of visual impairment. Treatments currently exist only for late-stage disease, while early and intermediate AMD lack validated functional endpoints suitable for treatment trials. This study will validate fundus-tracked dark adaptometry by determining its diagnostic accuracy, within-visit and between-visit repeatability, and longitudinal sensitivity to change. In addition, multimodal retinal imaging, blood-based biomarkers, metabolomics, proteomics, and AMD-related genetic variants will be assessed for their ability to predict or explain delayed dark adaptation. Healthy volunteers will undergo 2 visits (baseline and month 2); participants with early or intermediate AMD will undergo 3 visits (baseline, month 2, and month 18).

Inclusion Criteria:

• Written informed consent.
• All biological sexes and gender identities.
• Age >=18 years for healthy volunteers; age >=55 years for participants with AMD.
• Ability to understand German or English sufficiently for study information and procedures.

Additional Inclusion Criteria by Cohort:

Healthy Volunteers:

- No drusen >63 um and no subretinal drusenoid deposits in either eye.

Early AMD:

- Study eye with drusen >63 um but <125 um and no pigmentary changes.

Intermediate AMD:

- Study eye with drusen >125 um and/or pigmentary changes.

Exclusion Criteria:

• Claustrophobia relevant to dark-adaptation procedures.
• Hypersensitivity to indocyanine green or sodium iodide, iodine allergy, or hyperthyroidism.
• Known pregnancy.
• Study eye history of ocular surgery other than cataract surgery, YAG capsulotomy, or laser retinopexy.
• Ocular disease in the study eye that could affect visual function testing in the opinion of the investigators.
• Medical conditions or planned operations that could interfere with follow-up.
• Inability to comply with study procedures or insufficient language skills in the study language.
• Inability to provide informed consent.

Healthy volunteers and patients with early or intermediate AMD.

Upon completion of the study, the data will be made publicly available in an open science repository (e.g., Zenodo).