Ocular Outcomes of Combination Enzyme Replacement Therapy with Hematopoietic Cell Transplantation in Hurler Syndrome

Abstract

Purpose: Although hematopoietic cell transplantation (HCT) is an effective treatment for mucopolysaccharidosis type I (Hurler syndrome, MPS IH), it is unclear whether the additional use of enzyme replacement therapy (ERT) for further systemic improvement affects the ocular outcome. We performed a retrospective, observational clinical study to learn about the ocular outcomes of children receiving ERT before and after HCT for Hurler syndrome, MPS IH, compared to a matched control group receiving only HCT.

Methods: This single institution, retrospective study reviewed the ophthalmologic findings of children with MPS IH who were treated with recombinant a-L iduronidase ERT for 10-14 weeks prior to and 8 weeks following transplantation (combined therapy), compared with an age and transplant matched control group that did not receive ERT. The data collected included age, vision, and ocular examination details.

Results: Nine children in each cohort (ERT with HCT vs. HCT-only) were followed for 61.2 and 61.5 months, respectively. At last follow-up, mean best-corrected visual acuity in the ERT with HCT group was 0.45 logMAR below age-adjusted, normal acuity compared to 0.37 logMAR below age-adjusted normal acuity in the HCT group (p = 0.2650). The children in the combined therapy group performed optotype acuities at earlier ages than those undergoing only HCT (46 vs 73 months, p = 0.0041).

Conclusions: Visual outcomes in children with MPS 1H undergoing HCT do not appear to be better when ERT is given in conjunction with HCT when compared to a matched group receiving HCT alone. Longer follow-up with a large sample of patients may clarify the impact of ERT with HCT combination therapy for MPS IH.