Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations

NCT07265895 | Not Yet Recruiting

• 1 other identifier: IRDs-OSR
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Inherited Retinal Diseases (IRDs) are a heterogeneous group of genetically based degenerative retinal disorders, representing a major cause of visual impairment and blindness in working-age adults. Despite the approval of the first gene therapy for RPE65-related IRD (voretigene neparvovec) in 2017, most IRDs remain untreatable, though many gene therapies are in development. Effective trial design and therapy development require a deep understanding of disease natural history and genotype-phenotype correlations. Over 270 IRD-associated genes are known (e.g., ABCA4, USH2A, RPGR, PRPH2, BEST1), each linked to distinct phenotypes and clinical progression. This retrospective study analyzes clinical, functional, and imaging data (Optical Coherence Tomography, Fundus Autofluorescence, Microperimetry) from a large, genetically characterized IRD cohort at the IRCCS Ospedale San Raffaele up to December 31, 2025. The aims are to describe natural history, define genotype-phenotype relationships, and identify structural and functional outcome measures useful for future clinical trial endpoints, supporting personalized prognosis and trial design.

Conditions

Stargardt Disease; Retinal Degenerations; Retinitis Pigmentosa (RP)

Outcome Measures

Primary Outcomes (9)

• Best-corrected Visual Acuity

  Measured on measured Early Treatment Diabetic Retinopathy Study (ETDRS) charts and recorded in logMAR units

  through study completion, an average of 1 year

• Macular threshold sensitivity

  Measured in decibels using fundus- tracked MP (e.g., MAIA device) across a standard grid of 68 central loci under standardized mesopic conditions. Sensitivity deviation from age-matched normative values will also be computed

  through study completion, an average of 1 year

• Total Macular volume

  Measured in mm3 on OCT scans

  through study completion, an average of 1 year

• Centra Subfield Thickness

  Measured in micron on OCT scans

  through study completion, an average of 1 year

• Preserved Ellipsoid zone area

  Measured in mm2 on OCT scans

  through study completion, an average of 1 year

• Foveal Outer Nuclear Layer thickness

  Measured in microns on OCT scans

  through study completion, an average of 1 year

• Ellipsoid zone loss area

  Measured in mm2 on OCT scans

  through study completion, an average of 1 year

• Hyperautofluorescent (Robson- Holder) ring area

  Measured in mm2 on FAF images

  through study completion, an average of 1 year

• Dereased Autofluorescence area

  Measured in mm2 on Fundus autofluorescence images

  through study completion, an average of 1 year

Interventions

No Intervention: Observational Cohort OTHER

no intervention, natural history study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients affected by IRDs genetically confirmed

You may qualify if:

• Participant completed at least one ophthalmological and retinal imaging examination at our center.
• Clinically diagnosed with IRD, as per familiy history, clinical signs or symptoms, retinal imaging findings.
• Definitive genetic diagnosis of IRD with adequate molecular test

You may not qualify if:

• Affected by other retinal or optic nerve conditions potentially affecting analyses (diabetic retinopathy, glaucoma).
• History of retinotoxic medications (i.e., hydroxychloroquine, pentosan polysulfate sodium, tamoxifen, ritonavir, didanosine, MEK inhibitors) intake.
• Unclear genetic diagnosis.
• Incomplete or inadequate ophthalmological and imaging tests.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, Italy, 20132, Italy

Location

MeSH Terms

Conditions

Retinal Degeneration; Retinitis Pigmentosa; Stargardt Disease

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Retinal Dystrophies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Macular Degeneration

Central Study Contacts

Maurizio Battaglia Parodi, MD

CONTACT

00390226433545; battagliaparodi.maurizio@hsr.it

Lorenzo Bianco, MD

CONTACT

0039 0226433545; bianco.lorenzo@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 5, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)