Main objective: To characterize the phenotype, genetics and biology of myopic staphyloma in a European population (three countries involved).
Primary Outcome Measure:
The primary objective of this study is to identify genetic variants (SNPs) significantly associated with the presence of posterior staphyloma in individuals of European ancestry with high myopia.
A genome-wide association study (GWAS) will be conducted in 600 highly myopic Caucasian participants, divided into two well-phenotyped groups:
* 300 patients with posterior staphyloma (case group)
* 300 patients without posterior staphyloma (control group) SNP allele frequencies will be compared between the two groups using logistic regression models adjusted for relevant covariates (age, sex, axial length, and genetic ancestry via principal components).
The primary endpoint is the identification of SNPs s reaching genome wide significance (p \< 5×10-⁸)after correction for multiple testing.
Secondary Outcome Measures:
1. Functional annotation and biological pathway enrichment of associated loci Genome-wide significant SNPs will undergo functional annotation to identify nearby genes, regulatory regions, or non-coding variants with putative biological function.
Pathway and gene ontology enrichment analyses (e.g., KEGG, Reactome, GO) will be performed to highlight potential biological mechanisms contributing to posterior staphyloma pathogenesis.
2. Association with retinal imaging phenotypes Exploratory analyses will assess the relationship between genome wide significant variants and quantitative retinal imaging traits, including: subfoveal choroidal thickness,axial length,staphyloma depth, stpahyloma location, scleral curvature… These associations will be evaluated using multivariable linear regression models, adjusted for potential confounders.
3. Association with structural complications of posterior staphyloma Further exploratory analyses will investigate whether genome wide significant
SNPs are associated with major strutural complications of posterier staphyloma, such as :
macular atrophy,Bruch's membrane ruptures,choroidal neovascularization,foveoschisis, retinal detachment, visual fonction These analyses aim to uncover genetic markers linked to disease severity or progression
4. Differential expression of disease-relevant plasma/ serum protein biomarkers between groups, quantified by mass spectrometry, and correlated with clinical phenotype severity or progression (e.g., visual acuity loss, anatomical changes on OCT)
5. Efficiency and quality of iPSC reprogramming from peripheral blood mononuclear cells (PBMCs) in each study group, 4 individuals (1 male and 1 female myopic patient with staphyloma and 1 male and 1 female myopic patient without staphyloma, aged 30 to 35) assessed by reprogramming success rate, pluripotency marker expression, and genomic integrity. Derived iPSCs will be used differentiate retinal pigment epithelial cells in order to compare disease-relevant cellular phenotypes and functional responses in vitro.
