Delayed rod-mediated dark adaptation (RMDA), or delayed recovery of vision in a dark environment, is a functional biomarker (i.e., risk factor) for early age-related macular degeneration (AMD). This research plan is designed to elucidate the structural (anatomical) basis of this visual deficit using cellular- and subcellular level imaging of the retina and its supporting tissues in living people. An accurate map and timeline of structure-function relationships in persons tested for night vision will result in functionally validated structural endpoints for early AMD trials, as well as define major biologic effects for development into future treatments.

The Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2) is a prospective cohort study with baseline measurements that are repeated at follow-up 3 years later. The baseline and 3 year follow-up visits will each consist of 2 visits for a total of 4 visits.

Study assessments are listed below. All are collected at two visits at both baseline and follow-up for 4 visits total (blood collection for DNA analysis at baseline only). For some functional tests (photopic and mesonic acuity, photopic and mesonic contrast sensitivity), each eye will be tested separately. For other functional tests (dark-adapted two-color perimetry, light-adapted cone-mediate perimetry, rod-mediated dark adaptation), only one eye will be tested, which will be designated by the study eye. Tropicamide 1% and phenylephrine hydrochloride 2.5% are used to dilate pupils (diameter of ≥ 6 mm) as needed for specific parts of the protocol. After completing the baseline visits, participants will receive an annual phone call from the study coordinator so that contact information can be updated. Participants will receive an annual newsletter containing study related information (this will be submitted to the IRB for approval).

Study Assessments:

1. Rod-mediated dark adaptation (RMDA), the ability to recover light sensitivity after exposure to a bright light.
2. Dark-adapted two-color microperimetry, a measure of light sensitivity for lights of two different colors.
3. Photopic and mesopic acuity in central vision, as measured by letter charts..
4. Photopic and mesopic contrast sensitivity in central vision, as measured by letter charts..
5. Multimodal ocular imaging on both eyes, which consists of the following: color fundus photography, spectral domain optical coherence tomography (SDOCT), blue fundus autofluorescence (standard and quantitative), OCT-angiography (OCT-A).
6. Blood draw for the analysis of C-reactive protein, high-density lipoprotein, carotenoid level, DNA extraction, and examination of the presence of genetic risk associated with age-related macular degeneration (AMD).
7. Questionnaires: Demographics, medical co-morbidities, cognitive status screen, medication use, alcohol use, smoking, self-reported visual difficulty in the visual activities of daily living

The Young normal group will only complete:

1. Rod-mediated dark adaptation (RMDA), the ability to recover light sensitivity after exposure to a bright light.
2. Dark-adapted two-color microperimetry, a measure of light sensitivity for lights of two different colors.
3. . Photopic and mesopic acuity in central vision, as measured by letter charts..
4. Photopic and mesopic contrast sensitivity in central vision, as measured by letter charts..
5. Multimodal ocular imaging on both eyes, which consists of the following: color fundus photography, spectral domain optical coherence tomography (SDOCT), blue fundus autofluorescence (standard and quantitative),OCT-angiography (OCT-A).d and quantitative), OCT-angiography.

Inclusion Criteria:

For those in Normal Macular Health or Early AMD: aged ≥ 60 years; either have normal macular health in both eyes at baseline or have early AMD in one eye For Young Normals: aged 20-30 years old; normal macular health in both eyes.

Exclusion Criteria:

Exclusion for those in normal macular health are:

• ANY EYE CONDITION OR DISEASE IN EITHER EITHER (OTHER THAN EARLY CATARACT) THAT CAN IMPAIR VISION INCLUDING:
• diabetic retinopathy
• glaucoma
• ocular hypertension
• history of retinal diseases (e.g., retinal vein occlusion, retinal degenerations)
• optic neuritis
• corneal disease
• previous ocular trauma or surgery
• REFRACTIVE ERROR >- 6 DIOPTERS
• NEUROLOGICAL CONDITIONS THAT CAN IMPAIR VISION OR JUDGEMENT INCLUDING:
• multiple sclerosis
• Parkinson disease
• stroke
• Alzheimer disease
• seizure disorders
• brain tumor
• traumatic brain injury
• PSYCHIATRIC DISORDERS THAT COULD IMPAIR THE ABILITY:
• to follow simple directions
• answer questions about health and functioning
• or to provide informed consent
• DIABETES
• ANY MEDICAL CONDITION THAT CAUSES SIGNIFICANT FRALITY OR IS BELIEVED TO BE TERMINAL.

Exclusion criteria for the early AMD group:

These are identical to those described above, except that it is acceptable for participants to have early AMD (AREDS 2-4) in one eye and be AREDS grade 1 or any stage of AMD in the fellow eye.

Exclusion for Young Normals:

• ANY EYE CONDITION OR DISEASE IN EITHER EYE (OTHER THAN EARLY CATARACT) THAT CAN IMPAIR VISION INCLUDING:
• diabetic retinopathy
• glaucoma
• ocular hypertension
• history of retinal diseases (e.g., retinal vein occlusion, retinal degenerations)
• optic neuritis, corneal disease
• previous ocular trauma or surgery
• RERACTIVE ERROR >=6 DIOPTORS
• NEUROLOGICAL CONDITIONS THAT CAN IMPAIR VISION OR JUDGEMENT INCLUDING:
• multiple sclerosis
• Parkinson disease
• stroke
• Alzheimer disease
• seizure disorders
• brain tumor
• traumatic brain injury
• PSYCHIATRIC DISORDERS THAT COULD IMPAIR THE ABILITY TO:
• follow simple directions
• answer questions about health and functioning
• or to provide informed consent
• DIABETES
• ANY MEDICAL CONDITION THAT CAUSES SIGNIFICANT FRAILTY OR IS BELIEVED TO BE TERMINAL.

group 1 is >=60 years old with normal macular health group 2 is >=60 years old with early AMD group 3 is 20-30 years old are Young Normals

Currently there is no plan to make individual participant data available to other researchers.