Functionally Validated Structural Endpoints for Early AMD (ALSTAR2)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Age-related Macular Degeneration; Aging
• Intervention / Treatment: Other: Normal Macular Health; Other: Early Macular Degeneration; Other: Young Normals

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 556

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal Macular Health; >=60 years old with no macular disease	Other: Normal Macular Health; This group of participants will have function assessed using rod- and cone-mediated tests (rod-mediated dark adaptation, 2 color dark adapted perimetry, cone-mediated perimetry, photopic and mesopic acuity, photopic and mesopic contrast sensitivity). Age-related macular degeneration status will be determined by multi-modal imaging.
Early Macular Degeneration; >=60 years old with early age-related macular degeneration	Other: Early Macular Degeneration; This group of participants will have function assessed using rod- and cone-mediated tests (rod-mediated dark adaptation, 2 color dark adapted perimetry, cone-mediated perimetry, photopic and mesopic acuity, photopic and mesopic contrast sensitivity). Age-related macular degeneration status will be determined by multi-modal imaging.
Young Normals; 20-30 years old with normal macular health	Other: Young Normals; This group of participants will have function assessed using rod- and cone-mediated tests (rod-mediated dark adaptation, 2 color dark adapted perimetry, cone-mediated perimetry, photopic and mesopic acuity, photopic and mesopic contrast sensitivity). Age-related macular degeneration status will be determined by multi-modal imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rod-mediated dark adaptation	Time required to recover light sensitivity after exposure to bright light	Measured at baseline enrollment
Rod-mediated dark adaptation	Time required to recover light sensitivity after exposure to bright light	Measured at 3 years after baseline enrollment
incident age-related macular degeneration (AMD) or progression of AMD using multimodal imaging	development of AMD or progression of AMD at the 3 year follow up visit	Measured at baseline enrollment
incident age-related macular degeneration (AMD) or progression of AMD using multimodal imaging	development of AMD or progression of AMD at the 3 year follow up visit	Measured at 3 years after baseline enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Light sensitivity as measured by microperimetry and perimetry	Amount of light needed to detect a small target object	Measured at baseline enrollment
Light sensitivity as measured by microperimetry and perimetry	Amount of light needed to detect a small target object	Measured at 3 years after baseline enrollment
Photopic and mesopic acuity	Visual acuity under day time and twilight conditions	Measured at baseline enrollment
Photopic and mesopic acuity	Visual acuity under day time and twilight conditions	Measured at 3 years after baseline enrollment
Photopic and mesopic contrast sensitivity	Amount of contrast needed to recognize a letter under day time and twilight conditions	Measured at baseline enrollment
Photopic and mesopic contrast sensitivity	Amount of contrast needed to recognize a letter under day time and twilight conditions	Measured at 3 years after baseline enrollment

Collaborators and Investigators

• Sponsor: Cynthia Owsley
• Investigators: Principal Investigator: Cynthia Owsley, PhD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Curcio CA, McGwin G Jr, Sadda SR, Hu Z, Clark ME, Sloan KR, Swain T, Crosson JN, Owsley C. Functionally validated imaging endpoints in the Alabama study on early age-related macular degeneration 2 (ALSTAR2): design and methods. BMC Ophthalmol. 2020 May 19;20(1):196. doi: 10.1186/s12886-020-01467-0.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: vision; dark adaptation; retina; spectral domain optical coherence tomography; optical coherence tomography angiography; light sensitivity; quantitative autofluorescence
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: 1R01EY029595 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently there is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No