Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations, Monocentric Retrospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Best-corrected Visual Acuity
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Best-corrected Visual Acuity
时间窗: 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
时间窗: 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
时间窗: through study completion, an average of 1 year
Measured in mm3 on OCT scans
Centra Subfield Thickness
时间窗: through study completion, an average of 1 year
Measured in micron on OCT scans
Preserved Ellipsoid zone area
时间窗: through study completion, an average of 1 year
Measured in mm2 on OCT scans
Foveal Outer Nuclear Layer thickness
时间窗: through study completion, an average of 1 year
Measured in microns on OCT scans
Ellipsoid zone loss area
时间窗: through study completion, an average of 1 year
Measured in mm2 on OCT scans
Hyperautofluorescent (Robson- Holder) ring area
时间窗: through study completion, an average of 1 year
Measured in mm2 on FAF images
Dereased Autofluorescence area
时间窗: through study completion, an average of 1 year
Measured in mm2 on Fundus autofluorescence images
次要结局
未报告次要终点
研究者
Maurizio Battaglia Parodi
Associate Professor
IRCCS San Raffaele