Retinal Degenerations, Retinitis Pigmentosa (RP), Stargardt Disease
Conditions
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.
Interventions
OTHERNo Intervention: Observational Cohort
no intervention, natural history study
Sponsors
IRCCS San Raffaele
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Participant completed at least one ophthalmological and retinal imaging examination at our center. 2. Clinically diagnosed with IRD, as per familiy history, clinical signs or symptoms, retinal imaging findings. 3. Definitive genetic diagnosis of IRD with adequate molecular test
Exclusion criteria
1. Affected by other retinal or optic nerve conditions potentially affecting analyses (diabetic retinopathy, glaucoma). 2. History of retinotoxic medications (i.e., hydroxychloroquine, pentosan polysulfate sodium, tamoxifen, ritonavir, didanosine, MEK inhibitors) intake. 3. Unclear genetic diagnosis. 4. Incomplete or inadequate ophthalmological and imaging tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best-corrected Visual Acuity | through study completion, an average of 1 year | Measured on measured Early Treatment Diabetic Retinopathy Study (ETDRS) charts and recorded in logMAR units |
| Macular threshold sensitivity | through study completion, an average of 1 year | 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 |
| Total Macular volume | through study completion, an average of 1 year | Measured in mm3 on OCT scans |
| Centra Subfield Thickness | through study completion, an average of 1 year | Measured in micron on OCT scans |
| Preserved Ellipsoid zone area | through study completion, an average of 1 year | Measured in mm2 on OCT scans |
| Foveal Outer Nuclear Layer thickness | through study completion, an average of 1 year | Measured in microns on OCT scans |
| Ellipsoid zone loss area | through study completion, an average of 1 year | Measured in mm2 on OCT scans |
| Hyperautofluorescent (Robson- Holder) ring area | through study completion, an average of 1 year | Measured in mm2 on FAF images |
| Dereased Autofluorescence area | through study completion, an average of 1 year | Measured in mm2 on Fundus autofluorescence images |
Countries
Italy
Contacts
Primary ContactMaurizio Battaglia Parodi, MD
Backup ContactLorenzo Bianco, MD
Outcome results
None listed