Novel Quantification Methods for Fluorescence to Detect Progression in Stargardt Disease

Overview

The purpose of this study is to utilize flavoprotein fluorescence and fundus autofluorescence to detect progression of Stargardt macular dystrophy in a pediatric population over the course of a year with the hope of aiding future therapeutic risk-benefit decisions and assessment of outcomes.

Stargardt macular dystrophy is the most common of the juvenile-onset macular dystrophies. Despite determination of ABCA4 as the causative gene, clinicians have been challenged by variability in clinical phenotypes. Given the recent initiation of clinical trials to assess novel treatments (e.g. gene therapy), there is a need to identify patients with the worst prognosis.

The investigators have observed that pediatric patients lose central visual function faster than their adult counterparts. Thus, they present an ideal cohort with which to determine the utility of novel modalities to detect early change. These include flavoprotein fluorescence, a new imaging technique for detecting mitochondrial dysfunction developed at the University of Michigan. Fundus autofluorescence (FAF) is another commonly utilized technique of evaluating hereditary eye diseases. The investigators have developed a novel means of quantifying FAF signatures that will allow documentation of severity as well as detection of progression.

Full Title of Study: “Novel Quantification Methods for Fundus Flavoprotein Fluorescence and Lipofuscin Fluorescence to Detect Progression in Stargardt Disease”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: October 2016

Detailed Description

This study will evaluate whether more sophisticated testing and analytic methodologies, including fundus autofluorescence (FAF) and a novel non-invasive method to measure retinal flavoprotein fluorescence (FPF) may be used to better predict Stargardt macular dystrophy progression and monitor treatment effects than conventional modalities such visual acuity and visual field. This method involves the use of novel statistical methods to assess the heterogeneity of fundus autofluorescence images.

Participants will complete 3 visits to the University of Michigan Kellogg Eye Center. Each visit will take approximately 2.5 hours. The initial visit will include a routine clinical eye examination, measurement of best-corrected visual acuity, indirect ophthalmoscopy, microperimetry, frequency-domain optical coherence tomography, Goldmann visual fields, fundus flavoprotein fluorescence (FPF) imaging, and fundus autofluorescence (FAF) and fundus photography. Patients will return for evaluation at 6 and 12 months after their initial visit to repeat testing and imaging.

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline in pixel intensity quantification of fundus autofluorescence at 6 months
    • Time Frame: 0 months, 6 months
  • Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 6 months
    • Time Frame: 0 months, 6 months

Secondary Measures

  • Change from baseline in pixel intensity quantification of fundus autofluorescence at 12 months
    • Time Frame: 0 months, 12 months
  • Change from baseline in pixel intensity quantification of flavoprotein autofluorescence at 12 months
    • Time Frame: 0 months, 12 months

Participating in This Clinical Trial

Inclusion Criteria

  • Between the age of 5 and 18 years old
  • Clinical diagnosis of Stargardt Disease
  • Molecular confirmation of Stargardt Disease (with 2 identified mutations in ABCA4)
  • Visual acuity better than 20/100

Exclusion Criteria

  • Limited central vision, defined as visual acuity worse than 20/100
  • A diagnosis of any other retinal degenerative disease

Gender Eligibility: All

Minimum Age: 5 Years

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Michigan
  • Collaborator
    • Midwest Eye Banks
  • Provider of Information About this Clinical Study
    • Principal Investigator: K. Thiran Jayasundera, Assistant Professor, Retina and Uveitis – University of Michigan
  • Overall Official(s)
    • K. Thiran Jayasundera, MD, Principal Investigator, University of Michigan Kellogg Eye Center

References

Elner SG, Elner VM, Field MG, Park S, Heckenlively JR, Petty HR. Retinal flavoprotein autofluorescence as a measure of retinal health. Trans Am Ophthalmol Soc. 2008;106:215-22; discussion 222-4.

Field MG, Elner VM, Park S, Hackel R, Heckenlively JR, Elner SG, Petty HR. Detection of retinal metabolic stress resulting from central serous retinopathy. Retina. 2009 Sep;29(8):1162-6. doi: 10.1097/IAE.0b013e3181a3b923.

Field MG, Elner VM, Puro DG, Feuerman JM, Musch DC, Pop-Busui R, Hackel R, Heckenlively JR, Petty HR. Rapid, noninvasive detection of diabetes-induced retinal metabolic stress. Arch Ophthalmol. 2008 Jul;126(7):934-8. doi: 10.1001/archopht.126.7.934.

Chen B, Tosha C, Gorin MB, Nusinowitz S. Analysis of autofluorescent retinal images and measurement of atrophic lesion growth in Stargardt disease. Exp Eye Res. 2010 Aug;91(2):143-52. doi: 10.1016/j.exer.2010.03.021. Epub 2010 Apr 14.

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