Personalized Monitoring of Non-foveal, Non-vision Compromising Atrophic Age-related Macular Degeneration With Artificial Intelligence and Identification of Disease Progression (APENNINES)

Personalized Monitoring of Non-foveal, Non-vision Compromising Atrophic Age-related Macular Degeneration With Artificial Intelligence and Identification of Disease Progression in a Prospective, Multinational, Multicenter Observational Study

The goal of this prospective, multinational, multicenter observational study is to assess and predict progression in non-foveal, non-vision compromising atrophic AMD on an individual-based level over two years. The main objectives of this study are:

• Assess the individual progression rate of a patient in non-foveal, non-vision compromising atrophic AMD and assess personalized risk of progression based on imaging.
• Identify and quantify focal and global alterations in the retina in regard to disease progression.
• Evaluate the monitoring of AMD progression using approved AI algorithms.

All patients will be followed for 24 months with 6 month intervals to assess clinical changes. Monitoring of disease progression will be performed using the following routine in-vivo imaging procedures:

• Scanning Laser Fundus Photography
• Color Fundus Photography (CFP)
• Optical Coherence Tomography (OCT)
• Optical Coherence Tomography Angiography (OCTA)

Patients will be asked for their medical history. Standard ophthalmic examination, as well as a questionnaire on visual function will be carried out.

No intervention will be performed during the study since no treatment is yet available within Europe. As soon as treatment is approved in the EU, patients in this cohort might receive treatment according to availability in their respective country and standard of care. If treatment will be performed, it will be as standard of care outside the study according to each country's standard of care and by EMA label.

Study Overview

• Status: Recruiting
• Conditions: Age-Related Macular Degeneration; Geographic Atrophy

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Gregor Reiter, Priv.-Doz. Ing. DDr., BA MSc; Phone Number: +43 1 40400-73419; Email: gregor.reiter@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria
    • Not yet recruiting
    • Medical University of Vienna
    • Contact: Gregor S Reiter, Priv.-Doz. Ing. DDr., BA MSc; Phone Number: +4314040073419; Email: gregor.reiter@meduniwien.ac.at
• France
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Contact: Catherine Creuzot-Garcher, MD; Phone Number: +33380293756; Email: catherine.creuzot-garcher@chu-dijon.fr
• Slovenia
  • Ljubljana, Slovenia
    • Recruiting
    • University Medical Center Ljubljana
    • Contact: Polona Jaki-Mekjavic, MD; Phone Number: +38615221900; Email: polona.jakimekjavic@kclj.si
• Spain
  • Barcelona, Spain
    • Recruiting
    • Fundacio de Recerca Clinic Barcelona-Institut D Investigacions Biomed
    • Contact: Javier Zarranz-Ventura; Phone Number: +34617926250; Email: zarranz@clinic.cat
• Switzerland
  • Binningen, Switzerland
    • Recruiting
    • Vista Klinik Binningen
    • Contact: Katja Hatz; Phone Number: +41614266079; Email: Katja.Hatz@vista.ch
  • Zürich, Switzerland
    • Recruiting
    • University of Zurich
    • Contact: Daniel Barthelmes; Phone Number: +41432530598; Email: Daniel.Barthelmes@usz.ch
• United Kingdom
  • Belfast, United Kingdom
    • Recruiting
    • Queen's Unviversity Belfast
    • Contact: Ruth Hogg; Phone Number: +447734671087; Email: r.e.hogg@qub.ac.uk

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from each center's respective outpatient clinic and/or by referral from primary eye care (e.g. optometrist).

Description

Inclusion Criteria:

• Age: 55-99 years old
• Complete RPE and outer retinal atrophy (cRORA). This is (1) a region of hypertransmission of at least 250 µm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 µm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear.
• If both eyes are eligible, both eyes will be included in the cohort study.
• Clear optical media and adequate pupillary dilation for imaging and functional testin

Exclusion Criteria:

• Any surgical treatment of the eye within 3 months prior to baseline in the study eye
• History of anti-VEGF treatment in the study eye before baseline
• History of pseudophakic cystoid macular edema (Irvine Gass Syndrome) in the study eye
• History of uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) ≥ 25 mmHg despite treatment with IOP lowering medication), or C/D Ratio > 0.9
• Any concurrent intraocular condition in the study eye (e.g. advanced cataract or moderate/severe diabetic retinopathy) that, in the opinion of the investigator, will most likely require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition
• Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could cause an unwanted effect on treatment efficacy, compliance or require intraocular surgery (except for cataract surgery and YAG capsulotomy) during the study period
• Presence of corneal decompensation, haze or scarring with an impact on BCVA
• Refractive error larger than 6 diopters. In case of pseudophakia or refractive surgery: History of refractive error larger than 6 diopters.
• Intake of drugs known to cause retinal toxicity (e.g. hydroxychloroquine or tamoxifen)
• Presence of active macular neovascularization at baseline.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterise and quantify focal and global changes of the retina by retinal imaging to identify patients at risk for fast geographic atrophy (GA) progression	The association between biomarkers and GA progression will be assessed by linear mixed models. Artificial intelligence models will be applied to assess progression speed and predict local and global progression. Mixed Effects models will be calculated to estimate the association between the above mentioned independent variables, including the timepoint as an independent variable, on individual markers of progression (RPE and PR thinning). The r-squared value of the predicted increase in atrophy area will be used as an endpoint assessment to evaluate the predictive model.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify and quantify disease progression-related biomarkers	Longitudinal assessments of imaging biomarkers are performed in a descriptive manner. The following biomarkers will be evaluated in detail as independent variables: Hyperreflective Foci (HRF) (scale, nL); Drusen volume/Refractile drusen (scale, nL); Subretinal Drusenoid Deposits (SDD) (scale, mm2); PR loss/RPE loss ratio (scale, ratio); GA lesion size (mm2); Foveal involvement (categorical; yes or no); Thinning of outer retinal layers (PR thinning) (scale, µm); Other retinal biomarkers if relevant to the progression of GA The association between biomarkers and GA progression will be assessed by linear mixed models.	2 years
To evaluate monitoring AMD progression using approved AI algorithms.	The following will be provided by AI-based image analysis of the GA Monitor (independent variables): RPE integrity loss (mm2) in the 1mm central area, 6mm area, and the respective relative change to previous visit; PR integrity loss (mm2) in the 1mm central area, 6mm area, and the respective relative change to previous visit	2 years

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: University of Zurich; Centre Hospitalier Universitaire Dijon; Fundacion Clinic per a la Recerca Biomédica; Queen's University, Belfast; University Medical Centre Ljubljana; Vista Klinik

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Eye Diseases; Retinal Diseases; Retinal Degeneration; Disease Progression; Macular Degeneration; Geographic Atrophy
• Other Study ID Numbers: 1088/2024

Drug and device information, study documents

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