Evaluating the Relationship Between Function and Structure Using Data From a GA Natural History Cohort (ARCHERY)

Anatomical and Retinal CHanges Evaluated in Real-life GeographY Atrophy

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration that leads to progressive and irreversible vision loss. The course of visual decline varies widely among patients, and it is not always clear which anatomical features of the retina are associated with faster loss of vision.

This retrospective observational study aims to describe the natural history of vision loss in patients with geographic atrophy who have characteristics similar to those enrolled in recent clinical trials. The study will analyze previously collected clinical and imaging data from patients followed during routine clinical care at a single center.

The main goal of the study is to evaluate the relationship between changes in visual function and retinal anatomical features, such as the size and location of atrophic lesions and retinal layer integrity, using fundus autofluorescence and optical coherence tomography images.

No treatments or study procedures are performed as part of this research. All data used in the study were collected during standard clinical practice and analyzed retrospectively.

Study Overview

• Status: Completed
• Conditions: Geographic Atrophy; Age Related Macular Degeneration; AMD; Age Related Macular Degeneration (AMD); Geographic Atrophy Secondary to Age-related Macular Degeneration; Geographic Atrophy (GA) Secondary to Dry Age-related Macular Degeneration (AMD)

Detailed Description

This is a monocentric, retrospective observational study designed to evaluate the relationship between visual function and retinal anatomical features in a population with geographic atrophy (GA) secondary to dry age-related macular degeneration.

The study will analyze a natural history cohort identified from previously collected clinical and imaging data obtained during routine care at IRCCS Ospedale San Raffaele. Eligible eyes meet predefined inclusion and exclusion criteria consistent with those used in recent clinical trials, including well-demarcated GA lesions, preserved baseline visual acuity, and the absence of choroidal neovascularization or prior intravitreal treatment.

The primary objective is to estimate the proportion of eyes experiencing a loss of at least 15 ETDRS letters from baseline and to characterize the trajectory of visual acuity decline over time. Secondary objectives include the identification of baseline anatomical features associated with the risk and timing of significant visual loss, such as GA lesion size, foveal involvement, fundus autofluorescence patterns, lesion focality, and outer retinal layer thickness measured on optical coherence tomography.

Exploratory analyses will investigate the relationship between visual function decline and ellipsoid zone integrity metrics, where available, and will apply multivariable and machine learning-based models to explore non-linear associations between anatomical and functional parameters.

As this is a retrospective study, no investigational medicinal products, devices, or study-specific interventions are involved. All analyses are performed on pseudonymized or anonymized data derived from existing medical records and imaging archives. No additional patient contact, visits, or procedures are required.

• Study Type: Observational
• Enrollment (Actual): 60

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients aged 50 years or older with geographic atrophy secondary to dry age-related macular degeneration, identified retrospectively from a single tertiary referral center. The analysis includes eyes meeting predefined anatomical and functional criteria similar to those used in recent clinical trials, based on clinical records and retinal imaging collected during routine care.

Description

Inclusion Criteria:

• Male or female patients aged 50 years or older at baseline.
• Diagnosis of geographic atrophy secondary to dry age-related macular degeneration in the study eye.
• Well-demarcated geographic atrophy lesions confirmed by fundus autofluorescence imaging, with a total lesion area between 2.5 mm² and 17.5 mm².
• Presence of hyperautofluorescence in the junctional zone of the geographic atrophy lesion.
• Best-corrected visual acuity between 45 and 83 ETDRS letters at baseline.
• Availability of longitudinal clinical and imaging data with at least 6 months of follow-up.

Exclusion Criteria:

• Evidence or history of neovascular (wet) age-related macular degeneration in the study eye.
• Prior intravitreal therapy or systemic treatments specifically targeting age-related macular degeneration.
• Geographic atrophy lesions contiguous with peripapillary atrophy.
• Coexisting ocular diseases that could independently affect visual acuity or retinal structure.
• Incomplete or poor-quality clinical or imaging data precluding reliable assessment of study outcomes.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss of Best-Corrected Visual Acuity of ≥15 ETDRS Letters	Proportion of eyes experiencing a loss of at least 15 ETDRS letters from baseline best-corrected visual acuity. Visual acuity is measured using the ETDRS methodology under normal luminance conditions, based on clinical data collected during routine care.	From baseline to the last available follow-up visit, with a minimum follow-up of 6 months and a preferred follow-up of 12 to 15 months.

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele
• Collaborators: Annexon, Inc.

Publications and helpful links

General Publications

• David S Boyer; Protection Against Vision Loss by ANX007: Results from the Phase 2 ARCHER Clinical Trial. Invest. Ophthalmol. Vis. Sci. 2024;65(7):2791.
• Schmitz-Valckenberg S, Sahel JA, Danis R, Fleckenstein M, Jaffe GJ, Wolf S, Pruente C, Holz FG. Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study). Ophthalmology. 2016 Feb;123(2):361-368. doi: 10.1016/j.ophtha.2015.09.036. Epub 2015 Nov 3.
• Fleckenstein M, Mitchell P, Freund KB, Sadda S, Holz FG, Brittain C, Henry EC, Ferrara D. The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration. Ophthalmology. 2018 Mar;125(3):369-390. doi: 10.1016/j.ophtha.2017.08.038. Epub 2017 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: optical coherence tomography; age-related macular degeneration; geographic atrophy; fundus autofluorescence; structure-function correlations
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Geographic Atrophy
• Other Study ID Numbers: ARCHERY (Other Identifier: San Raffaele Hospital)

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: No