Retinal Fundus Flavoprotein Fluorescence in Age Related Macular Degeneration (FPF in AMD)

Retinal Fundus Flavoprotein Fluorescence in Age Related Macular Degeneration: New Insights From Multimodal Imaging

The goal of this clinical trial is to learn if the areas of stressed cells in the retina correlate to areas of disease identified in standard imaging and whether the images are helpful to identify potential areas of concern before symptoms or disease occurs. The main question it aims to answer is:

• to evaluate patterns of increased autofluorescence FPF in the setting of geographic atrophy

Participants will undergo FPF imaging using the OcuMet Beacon system.

Study Overview

• Status: Completed
• Conditions: Age-Related Macular Degeneration; Geographic Atrophy
• Intervention / Treatment: Device: OcuMet Beacon

Detailed Description

The goal of this clinical trial is to learn if areas of mitochondrial functional distress in the macula (as imaged using fundus flavoprotein fluorescence) correlate with areas of anatomic disease identified on standard fundus autofluorescence (FAF) imaging.

The study aims to evaluate patterns of anomalous fundus flavoprotein fluorescence (FPF) in patients with advanced geographic atrophy (GA) due to dry age-related macular degeneration.

Participants will undergo FPF imaging using the OcuMet Beacon system and FAF imaging using Heidelberg Spectralis.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Department of Ophthalmology and Visual Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 50 years or older and may be either male or female of any race
• Established diagnosis of GA due to AMD
• GA characteristics: GA area of between 1.25 mm² and 23 mm², with seventy percent of eyes having GA area ranging from 2.5 mm2 to 17.5 mm2. GA may be unifocal or multifocal. GA may be subfoveal or extrafoveal, with twenty-five percent of eyes having subfoveal GA. The presence of concurrent peripapillary atrophy will not exclude subjects from participation
• Willing to participate as evidenced by signing the written informed consent

Exclusion Criteria:

• Unable to tolerate ophthalmic imaging
• Presence of neovascular AMD on OCT as confirmed by an ophthalmologist
• Presence of significant media opacity preventing adequate retinal imaging
• Presence of concurrent retinal disease which may confound assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fundus autofluorescence (FAF) imaging	Device: OcuMet Beacon; OcuMet Beacon is a novel fundus camera the can detect, capture, and assess FPF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optical Coherence Tomography (OCT) Variables	Ellipsoid Zone (EZ) loss refers to damaged photoreceptors in the eye. Retinal Pigment Epithelium (RPE) are cells that nourish photoreceptors in the eye, RPE loss is a measure of the degradation of these cells. Geographic Atrophy (GA) is an advanced stage of macular degeneration. These OCT variables are measured in millimeters squared from images taken with the Heidelberg Spectralis.	up to 45 minutes
Flavoprotein Fluorescence (FPF) Intensity	Average pixel intensity over a 5.5 mm-diameter region centered at the macula, a measure of oxidative stress. Data range from 0-100 where higher numbers indicate more severe disease. This is measured with the OcuMet Beacon.	Up to 45 minutes
FPF Heterogeneity	This is a measure of variability in retinal mitochondrial flavoprotein fluorescence (FPF) across the macula. It is a parameter that measures distribution and spatial variability of fluorescent signal by quantifying signal distribution of energy in localized hotspots, normalized to background. Normal values are less than 1 AU (arbitrary units), with values higher than 1 AU (in the range of 1-10 AU) corresponding to increased levels of metabolic distress due to oxidized mitocondria within the particular area of the retina that was imaged. This is measured with the OcuMet Beacon.	up to 45 minutes
Correlation Between FPF-intensity, FPF-heterogeneity and OCT Continuous Variables	Spearman's rank coefficient was chosen as the primary metric due to the relatively small number of eyes in our sample as well as the lack of normally-distributed data (confirmed by Shapiro-Wilk tests, evaluated at α=0.05). Correlations were calculated between both FPF biomarkers and all FAF/OCT variables (i.e. areas of GA, EZ loss, and RPE loss). To account for correlation between eyes belonging to the same patient, p-values were obtained via nonparametric bootstrap resampling at the patient level.	up to 45 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the Cross-sectional Associations Between FPF Intensity to FAF Area at the Time of Measurement	FPF Intensity is the average pixel intensity over a 5.5 mm-diameter region centered at the macula (measured in gray scale units) compared to are of Geographic Atrophy (measured in millimeters squared). Spearman's rank coefficient was chosen as the primary metric due to the relatively small number of eyes in our sample as well as the lack of normally-distributed data (confirmed by Shapiro-Wilk tests, evaluated at α=0.05).	Up to 45 minutes
Compare the Cross-sectional Associations Between Best Corrected Visual Acuity (BCVA - Using Early Treatment Diabetic Retinopathy Study, Greater Number of Letters Read Correctly Equals Better Vision) to FAF Area at the Time of Measurement		Up to 45 minutes
Correlation Between FPF-intensity, FPF-heterogeneity and Participant Variables	Spearman's rank coefficient was chosen as the primary metric due to the relatively small number of eyes in our sample as well as the lack of normally-distributed data (confirmed by Shapiro-Wilk tests, evaluated at α=0.05). Correlations were calculated between both FPF biomarkers and all continuous demographic and FAF/OCT variables (i.e. age and logMAR values). To account for correlation between eyes belonging to the same patient, p-values were obtained via nonparametric bootstrap resampling at the patient level. Participant variables are reported in the baseline characteristics section.	up to 45 minutes

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Mihai Mititelu, MD, MPH, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): May 27, 2025

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Geographic Atrophy
• Other Study ID Numbers: 2023-1715; A536000 (Other Identifier: UW Madison); SMPH/OPHTHAL&VIS SCI/GEN (Other Identifier: UW- Madison); Protocol Version 11/6/2024 (Other Identifier: UW- Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No