Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants

Fahnehjelm, Kristina Teär; Olsson, Mariann; Chen, Enping; Hengstler, Jürg; Naess, K; Winiarski, Jacek

doi:10.1111/apa.14368

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…The very long-term and standardized follow-up data, analyzed with a mixed model, allowed us to unite contradictory results of previous studies showing both improvement and worsening of corneal clouding after HCT [1,4,5,12]. Most studies only evaluated 1 particular time point or at a short time after HCT, resulting in different conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…However, even though patients are undergoing HCT as early as possible and transplantation protocols have been optimized, resulting in normal hematologic enzyme activity in most patients, residual disease remains substantial and diminishes the quality of life [5,7,11]. Whether this is also true for ocular manifestations remains uncertain; previous studies have shown both improvement and worsening of the ocular phenotype in patients with MPS-1 after HCT [1,5,12]. Routine follow-up over a time span of more than 10 years at the Sylvia Toth Center for Multidisciplinary Follow-Up after Hematopoietic Cell Transplantation in the Wilhelmina Children's Hospital, Utrecht, The Netherlands, allowed us to explore this question.…”

Section: Introductionmentioning

confidence: 99%

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

Broek

Egmond-Ebbeling

Achterberg

et al. 2020

Biology of Blood and Marrow Transplantation

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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 a-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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Broek

Egmond-Ebbeling

Achterberg

et al. 2020

Biology of Blood and Marrow Transplantation

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“…Ocular motility abnormalities are common, especially exotropia, secondary to decreased corneal opacity and GAG deposition in the extra-ocular muscles [1,9,10]. Other case reports and studies note retinopathies in all three MPS I syndromes [1,10,16,17]. Visual changes from optic neuropathies and retinopathies may go unnoticed due to the overlying corneal clouding.…”

Section: Mps Imentioning

confidence: 99%

“…Currently, there are four available ERTs—Aldurazyme ® (BioMarin Pharmaceutical Inc., Novato, CA, USA) for MPS I, Elaprase ® (Shire Human Genetic Therapies Inc., Cambridge, CA, USA) for MPS II, Vimizim ® (BioMarin Pharmaceutical Inc., Novato, CA, USA ) for MPS IVA, and Naglazyme ® (BioMarin Pharmaceutical Inc., Novato, CA, USA) for MPS VI [17].…”

Section: Hematopoietic Stem Cell Transplant and Enzyme Replacemenmentioning

confidence: 99%

Ophthalmological Findings in Mucopolysaccharidoses

Tomatsu

Pitz

Hampel

2019

JCM

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The mucopolysaccharidoses (MPS) are a heterogenous group of lysosomal storage disorders caused by the accumulation of glycosaminoglycans (GAGs). The accrual of these compounds results in phenotypically varied syndromes that produce multi-organ impairment with widespread systemic effects. The low incidence of MPS (approximately 1/25,000 live births) in conjunction with the high childhood mortality rate had limited the availability of research into certain clinical features, especially ocular manifestations. As the recent successes of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have greatly increased life expectancy in these patients, they have served as a focal point for the transition of research towards improvement of quality of life. Ophthalmological findings in MPS include corneal clouding, glaucoma, optic neuropathies, and retinopathies. While corneal clouding is the most common ocular feature of MPS (especially type I, IVA, and VI), its response to HSCT and ERT is minimal. This review discusses known eye issues in the MPS subtypes, diagnosis of these ocular diseases, current clinical and surgical management, noteworthy research progress, and ultimately presents a direction for future studies.

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“…Corneal clouding may progress despite systemic therapy [ 5 ]. In a 2018 study by Fahnehjelm et al [ 45 ], which studied eight patients with MPS I Hurler Syndrome, corneal opacities were present in all patients before or shortly after beginning therapy with HSCT. The clouding increased during follow up, despite HSCT, in 5/8 patients.…”

Section: Systemic Therapies and Their Effect On Corneal Cloudingmentioning

confidence: 99%

Management of Corneal Clouding in Patients with Mucopolysaccharidosis

McGrath

Ashworth

2021

JCM

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Mucopolysaccharidoses (MPS) are a rare group of lysosomal storage disorders characterized by the accumulation of incompletely degraded glycosaminoglycans (GAGs) in multiple organ systems including the eye. Visual loss occurs in MPS predominantly due to corneal clouding and retinopathy, but the sclera, trabecular meshwork and optic nerve may all be affected. Despite the success of therapies such as enzyme replacement therapy (ERT) and hematopoietic stem-cell transplantation (HSCT) in improving many of the systemic manifestations of MPS, their effect on corneal clouding is minimal. The only current definitive treatment for corneal clouding is corneal transplantation, usually in the form of a penetrating keratoplasty or a deep anterior lamellar keratoplasty. This article aims to provide an overview of corneal clouding, its current clinical and surgical management, and significant research progress.

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Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants

Abstract: Despite HSCT, the long-term follow-up of patients with MPS IH showed reduced visual acuity due to corneal opacities or retinal degeneration.

Cited by 8 publications

References 27 publications

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

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

Ophthalmological Findings in Mucopolysaccharidoses

Management of Corneal Clouding in Patients with Mucopolysaccharidosis

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