부산대학교 도서관

Aim Corneal clouding is seen in nearly all patients with Mucopolysaccharidosis-1 (MPS-1) causing visual impairment. Hematopoietic cell transplantation (HCT) is able to stabilize disease in many organs including the brain. However, residual disease in peripheral tissues is often described. Therefore, the aim of this study was to determine the long-term effect of HCT on ocular disease in MPS-1 patients. Methods Corneal clouding (grade 0-4) and visual acuity (Decimal scale) were prospectively collected from all consecutive MPS-1 patients treated with HCT between 2003 and 2018 at the UMC Utrecht. The primary outcomes of interest, the effect of time on corneal clouding and visual acuity, were analyzed using a linear mixed model. The correlation between corneal clouding and visual acuity was analyzed with Pearson's rho. Other parameters studied were clinical phenotype, age at time of transplantation and hematological enzyme level after transplantation. Other outcomes of interest analyzed included intra-ocular pressure, refraction, and macula and lens abnormalities. Results 24 successfully engrafted MPS-1 patients were included (92% with >95% chimerism and normal enzyme levels after HCT). Corneal clouding stabilized during the first years after HCT, but increased rapidly beyond three years (figure 1). Other predictors for increased corneal clouding were age at time of transplantation (0.74, 95%CI 0.34:1.15; p=0.0026) and clinical phenotype (−1.02, 95%CI −0.18:−1.86; p=0.0335). Visual acuity also worsened significantly over time (−0.03, 95%CI −0.06:−0.007; p=0.01). Corneal clouding was strongly negatively correlated with visual acuity (ρ −0.60, p = 7.12e−11). Conclusion After initial stabilization, ongoing ocular disease is seen in MPS-1 patients despite successful HCT. This hallmarks the shortcomings of current standard therapies. New therapies that overcome the weak spots of these therapies are necessary to improve the late outcomes of these patients. [ABSTRACT FROM AUTHOR]