Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14.

Schönbach EM; Strauss RW; Ibrahim MA; Janes JL; Birch DG; Cideciyan AV; Sunness JS; Muñoz B; Ip MS; Sadda SR; Scholl HPN

doi:10.1016/j.ajo.2020.03.020

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Journal article

Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14.

Schönbach EM Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, USA.
Strauss RW Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Kepler University Clinic, Linz, Linz, Austria; Department of Ophthalmology, Medical University of Graz, Graz, Austria.
Ibrahim MA Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Byers Eye Institute, Stanford University, Palo Alto, California, USA.
Janes JL University Hospitals Clinical Research Center, Cleveland Medical Center, Cleveland, Ohio, USA.
Birch DG Retina Foundation of the Southwest, Dallas, TX, USA.
Cideciyan AV Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sunness JS Greater Baltimore Medical Center, Baltimore, Maryland, USA.
Muñoz B Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ip MS Doheny Eye Institute, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA.
Sadda SR Doheny Eye Institute, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA.
Scholl HPN Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; Department of Ophthalmology, University of Basel, Basel, Switzerland. Electronic address: Hendrik.Scholl@usb.ch.

2020-03-31

Published in:

American journal of ophthalmology. - 2020

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English PURPOSE
Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.

DESIGN
Multicenter, international, prospective cohort study: ProgStar Study.

METHODS
Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).

RESULTS
Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).

CONCLUSIONS
In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

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