Clinical trial NCT02583152: New Imaging Technology to Assess Effect of Enzyme Replacment Therapy on Eye Disease Progession in Mucopolysacchardiosis
Official title: Use of New Imaging Technology to Assess Effect of Enzyme Replacment Therapy on Eye Disease Progession in Mucopolysacchardiosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Mucopolysaccharidoses
Lead sponsor: Manchester Royal Eye Hospital
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2015-10-22
Enrollment: 50
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Adult and paediatric participants with MPS and corneal opacification will be potentially eligible for this study, including those untreated, treated with previous haematopetic stem cell transplant, and treated with ERT.
* Participants who have a confirmed diagnosis of mucopolysaccharosisis type I (Hurler, Hurler/Scheie and Scheie), MPS type II (Hunter), type III (Sanfilippo) type IV (Morquio) and type VI (MaroteauxLamy), type VII (Sly) will be eligible if able to hold relatively still while seated at an instrument with a head rest.

Brief summary: Mucopolysaccharidoses (MPS) are currently treated with Enzyme replacement therapy and Bone Marrow Transplantation (BMT). No current evidence on the effectiveness on these therapies on the eye in this systemic disease is avalible. Using new imaging techniques; previously subjective data can be quantified and compared to determine if there is an improvment in the vision of patients with MPS.

Detailed description: The mucopolysaccharidoses (MPS) are a group of hereditary disorders which arise from defects in enzymes which break down glycosaminoglycans (GAGs) which occur in a wide variety of tissues, resulting in multiple systemic complications. Sight loss occurs in MPS due to corneal clouding, retinal degeneration, glaucoma and damage to the optic nerve. Corneal opacification occurs in infancy in several MPS subtypes and in the untreated disease the opacification is thought to be progressive, contributing to significant visual impairment in many patients. Improvements in quality of life and lifespan as a result of early treatment (with enzyme replacement therapy and haematopoetic stem cell transplantation) have meant that management of ocular complications and preservation of vision has increased importance.

A repeatable, reliable technique for quantification of corneal clouding will allow objective demonstration of the effect of treatments such as ERT in stabilisation or improvement of corneal clouding, and to establish the natural history of corneal opacification in MPS.

The investigators have previously developed the Iris camera (Irisguard Corp, McLean, VA 22102, USA) technology to give an objective measure of corneal clouding (Irisguard model IGAD100 ®) (Aslam et al 2009). The investigators demonstrated that use of the iris camera for corneal opacification assessment in MPS is feasibile, practical and has shown evidence for validity and reliability (Aslam et al 2012) (research funded in part by Biomarin Europe Ltd). The densitometry program for the Pentacam® Scheimpflug camera has also been shown to be able to provide measurements of corneal clouding in MPS .This research proposal will allow us to use to these techniques to quantify corneal clouding over time in MPS patients and to assess the effects of treatment with ERT and HSCT on corneal opacification.

Eligibility criteria: Inclusion Criteria:

* Adult and paediatric participants with MPS and corneal opacification will be potentially eligible for this study, including those untreated, treated with previous haematopetic stem cell transplant, and treated with ERT.
* Participants who have a confirmed diagnosis of mucopolysaccharosisis type I (Hurler, Hurler/Scheie and Scheie), MPS type II (Hunter), type III (Sanfilippo) type IV (Morquio) and type VI (MaroteauxLamy), type VII (Sly) will be potentially eligible. In order to cooperate with the examinations, the participant needs to be able to hold relatively still while seated at an instrument with a head rest and hold fixation for several seconds for this reason participants over the age of 3 years will be eligible.

Exclusion Criteria:

* Those who are aged under 3 years or who have significant neurological involvement which would influence understanding and/or cooperation.

Primary outcomes:
measure: Corneal densitometry scores in participants on treatment
timeFrame: 60 months study period
Secondary outcomes:
measure: Corneal clouding score over time in patients on treatment.
timeFrame: 60 months study period
Other outcomes:
measure: Repeatability and accessibility for each imaging technique
timeFrame: 60 months study period
measure: Retinal morphology changes with Optos wide field digital imaging and high resolution OCT
timeFrame: 60 months study period
Locations:
city: Manchester
country: United Kingdom
facility: Manchester Royal Eye Hospital
Study officials:
affiliation: Central Manchester Foundation Trust
name: Jane Ashworth, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: