Longitudinal Analysis of Ocular Disease in Children with Mucopolysaccharidosis I after Hematopoietic Cell Transplantation

Brigitte T A van den Broek; Michelle B van Egmond-Ebbeling; Jens A Achterberg; Jaap Jan Boelens; Isa C Vlessert; Hubertus C M T Prinsen; Jaap van Doorn; Peter M van Hasselt

doi:10.1016/j.bbmt.2019.11.025

Longitudinal Analysis of Ocular Disease in Children with Mucopolysaccharidosis I after Hematopoietic Cell Transplantation

Biol Blood Marrow Transplant. 2020 May;26(5):928-935. doi: 10.1016/j.bbmt.2019.11.025. Epub 2019 Nov 29.

Authors

Brigitte T A van den Broek¹, Michelle B van Egmond-Ebbeling², Jens A Achterberg³, Jaap Jan Boelens⁴, Isa C Vlessert⁵, Hubertus C M T Prinsen⁵, Jaap van Doorn⁵, Peter M van Hasselt⁶

Affiliations

¹ Sylvia Toth Center for Multidisciplinary Follow-Up after Hematopoietic Cell Transplantation, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Section Metabolic Diseases, Department of Child Health, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: [email protected].
² Sylvia Toth Center for Multidisciplinary Follow-Up after Hematopoietic Cell Transplantation, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: [email protected].
³ Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Sylvia Toth Center for Multidisciplinary Follow-Up after Hematopoietic Cell Transplantation, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Pediatric Blood and Marrow Transplantation Program, Memorial Sloan Kettering Cancer Center, New York, New York.
⁵ Section of Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Sylvia Toth Center for Multidisciplinary Follow-Up after Hematopoietic Cell Transplantation, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Section Metabolic Diseases, Department of Child Health, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address: [email protected].

PMID: 31786241
DOI: 10.1016/j.bbmt.2019.11.025

Abstract

Corneal clouding, causing visual impairment, is seen in nearly all patients with mucopolysaccharidosis type 1 (MPS-1). Hematopoietic cell transplantation (HCT) is able to stabilize disease in many organs. Residual disease in several tissues is being increasingly recognized, however. Data on the effect of HCT on ocular disease in patients with MPS-1 are contradictory. With this study, we aim to clarify the long-term effects of HCT on ocular disease in these patients. Best corrected visual acuity (BCVA), refraction, intraocular pressure (IOP), and slit-lamp biomicroscopic and fundoscopic examinations, including corneal clouding, were collected prospectively from 24 patients with MPS-1 who underwent HCT successfully between 2003 and 2018 (92% with >95% chimerism and normal enzyme activity after HCT). The course of corneal clouding and BCVA after HCT were analyzed using a linear mixed model. Other parameters studied were clinical phenotype, age at time of transplantation, and hematologic enzyme activity after transplantation. Outcomes of additional ophthalmologic tests were described. In addition, IDUA and α-galactosidase A (AGAL) enzyme activity and glycosaminoglycan (GAG) concentration in tear fluid were determined. Corneal clouding stabilized in the first years after HCT but increased rapidly beyond 3 years (P < .0001). BCVA and IOP also worsened over time (P = .01 and P < .0001, respectively). IDUA activity in tear fluid remained very low (P < .0001). After initial stabilization in the cornea, ongoing ocular disease and low IDUA activity in tear fluid is seen in patients with MPS-1 despite treatment with HCT, unveiling a weak spot of current standard therapy. New therapies that overcome these shortcomings are needed to improve the late outcomes of patients.

Keywords: HCT; MPS; disease progression; metabolic diseases; ocular features.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Cornea
Hematopoietic Stem Cell Transplantation*
Humans
Intraocular Pressure
Mucopolysaccharidosis I* / therapy
Phenotype