X-linked retinoschisis Clinical characteristics and outcome of medical and surgical treatment

This doctoral thesis focuses on X-linked retinoschisis (XLRS), a congenital inherited retinal dystrophy that predominantly affects males and is caused by pathogenic variants in the RS1 gene. A lack of functional retinoschisin impairs retinal cellular adhesion, resulting in characteristic macular cystoid fluid collections (CFC) and slowly progressive visual impairment. The primary aim of this research is to advance understanding of the disease, establish robust clinical outcome measures, and enhance trial readiness for future gene therapy studies. A central component of this work is the development and validation of deep-learning models that automatically and objectively quantify the volume of cystoid fluid collections on optical coherence tomography (OCT) scans. This artificial intelligence–quantified schisis volume serves as a sensitive structural endpoint that could substantially reduce the sample sizes required for clinical trials. Furthermore, this thesis evaluates the management and surgical outcomes of severe vitreoretinal complications, specifically vitreous haemorrhage and retinal detachment. It also investigates the efficacy and safety of carbonic anhydrase inhibitors, including acetazolamide, through a retrospective study, a randomised controlled trial (the AXIS trial), and a crossover extension study (the REAXIS study). Finally, this thesis presents the clinical characterisation of a novel, previously undescribed hereditary macular entity identified in a Dutch family: pseudocolobomatous autosomal dominant atrophic maculopathy (PADAM).
Together, these findings address critical knowledge gaps in diagnostic imaging, complication management, and treatment evaluation, thereby laying a solid foundation for future therapeutic interventions in XLRS.