The Progression of Stargardt Disease Using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15

Etienne M Schönbach; Lucas Janeschitz-Kriegl; Rupert W Strauss; Marco E G V Cattaneo; Kaoru Fujinami; David G Birch; Artur V Cideciyan; Janet S Sunness; Richard G Weleber; Michael S Ip; SriniVas R Sadda; Hendrik P N Scholl; ProgStar Study Group

doi:10.1016/j.ajo.2021.04.015

The Progression of Stargardt Disease Using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15

Am J Ophthalmol. 2021 Oct:230:123-133. doi: 10.1016/j.ajo.2021.04.015. Epub 2021 May 2.

Affiliations

¹ From the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA; University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio, USA.
² Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; Departments of Ophthalmology, University of Basel, Basel, Switzerland.
³ From the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA; Moorfields Eye Hospital, London, United Kingdom; Department of Ophthalmology, Johannes Kepler University, Linz, Austria; Department of Ophthalmology, Medical University, Graz, Austria; UCL Institute of Ophthalmology, London, United Kingdom.
⁴ Clinical Research, University of Basel, Basel, Switzerland.
⁵ Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
⁶ Retina Foundation of the Southwest, Dallas, Texas, USA.
⁷ Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, Baltimore, Maryland, USA.
⁹ Casey Eye Institute, Oregon Retinal Degeneration Center, Oregon Health & Science University, Portland, Oregon, USA.
¹⁰ Doheny Eye Institute, Los Angeles, California, USA; UCLA David Geffen School of Medicine, Los Angeles, California, USA.
¹¹ Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; Departments of Ophthalmology, University of Basel, Basel, Switzerland. Electronic address: Hendrik.Scholl@iob.ch.

PMID: 33951446
DOI: 10.1016/j.ajo.2021.04.015

Abstract

Purpose: To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity.

Methods: Design: International, multicenter, prospective cohort study with 5 study visits every 6 months over 24 months.

Participants: A total of 233 individuals with genetically confirmed STGD1 (≥1 disease-causing ABCA4 variant).

Main outcome measures: The total volume (V_TOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of V_TOT over time and its correlation with the ABCA4 genotype and baseline features.

Results: At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average V_TOT of 0.91 decibel-steradian (dB-sr) and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% confidence interval] was 0.077 [0.064, 0.090] dB-sr/y for V_TOT and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of V_TOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline V_TOT; P < .001) and exhibited a difference in the first vs second year of follow-up (0.065 dB-sr/year vs 0.089 dB-sr/year, respectively; P < .001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (P < .001), whereas a significant association with the genotype was not detected (P = .7).

Conclusion: In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

ATP-Binding Cassette Transporters / genetics
Adult
Disease Progression
Humans
Prospective Studies
Retina* / diagnostic imaging
Stargardt Disease
Tomography, Optical Coherence
Visual Acuity
Visual Field Tests
Visual Fields*

Substances

ABCA4 protein, human
ATP-Binding Cassette Transporters