Age-Related Macular Degeneration, Geographic Atrophy
Conditions
Brief summary
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.
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.
Interventions
DEVICEOcuMet Beacon
OcuMet Beacon is a novel fundus camera the can detect, capture, and assess FPF.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optical Coherence Tomography (OCT) Variables | up to 45 minutes | 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. |
| Flavoprotein Fluorescence (FPF) Intensity | Up to 45 minutes | 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. |
| FPF Heterogeneity | up to 45 minutes | 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. |
| Correlation Between FPF-intensity, FPF-heterogeneity and OCT Continuous Variables | up to 45 minutes | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Cross-sectional Associations Between FPF Intensity to FAF Area at the Time of Measurement | Up to 45 minutes | 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). |
| 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 | up to 45 minutes | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMihai Mititelu, MD, MPH
University of Wisconsin, Madison
Participant flow
Recruitment details
Participants who were enrolled in 2023-0958 (NCT05961332) and met the inclusion criteria were recruited to this study from April 2024 to May 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 78.308 years STANDARD_DEVIATION 7.047 |
| Best Corrected Visual Acuity (BCVA) | 0.456 logMAR STANDARD_DEVIATION 0.314 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Laterality Both Eyes | 15 Participants |
| Laterality Single Eye | 11 Participants |
| Lens Status Phakic | 18 eyes |
| Lens Status Pseudophakic | 23 eyes |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
None listed