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.
Study Type
OBSERVATIONAL
Enrollment
200
no intervention, natural history study
IRCCS Ospedale San Raffaele
Milan, Italy, Italy
Best-corrected Visual Acuity
Measured on measured Early Treatment Diabetic Retinopathy Study (ETDRS) charts and recorded in logMAR units
Time frame: 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
Time frame: through study completion, an average of 1 year
Total Macular volume
Measured in mm3 on OCT scans
Time frame: through study completion, an average of 1 year
Centra Subfield Thickness
Measured in micron on OCT scans
Time frame: through study completion, an average of 1 year
Preserved Ellipsoid zone area
Measured in mm2 on OCT scans
Time frame: through study completion, an average of 1 year
Foveal Outer Nuclear Layer thickness
Measured in microns on OCT scans
Time frame: through study completion, an average of 1 year
Ellipsoid zone loss area
Measured in mm2 on OCT scans
Time frame: through study completion, an average of 1 year
Hyperautofluorescent (Robson- Holder) ring area
Measured in mm2 on FAF images
Time frame: through study completion, an average of 1 year
Dereased Autofluorescence area
Measured in mm2 on Fundus autofluorescence images
Time frame: through study completion, an average of 1 year
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