Etienne M Schönbach1, Rupert W Strauss2, Mohamed A Ibrahim3, Jessica L Janes4, David G Birch5, Artur V Cideciyan6, Janet S Sunness7, Beatriz Muñoz8, Michael S Ip9, SriniVas R Sadda9, Hendrik P N Scholl10. 1. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, United States. 2. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Kepler University Clinic, Linz, Linz, Austria; Department of Ophthalmology, Medical University of Graz, Graz, Austria. 3. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Byers Eye Institute, Stanford University, Palo Alto, CA, United States. 4. University Hospitals Clinical Research Center, Cleveland Medical Center, Cleveland, OH, United States. 5. Retina Foundation of the Southwest, Dallas, TX, United States. 6. Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, United States. 7. Greater Baltimore Medical Center, Baltimore, MD, United States. 8. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States. 9. Doheny Eye Institute, UCLA David Geffen School of Medicine, Los Angeles, CA, United States. 10. Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; Department of Ophthalmology, University of Basel, Basel, Switzerland. Electronic address: Hendrik.Scholl@usb.ch.
Abstract
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. Here, we hypothesize that the functional decline is faster at the edge of the dense scotoma (eMS) than using overall MS. DESIGN: Multicenter, international, prospective cohort study: ProgStar study (NCT01977846). METHODS: Stargardt disease patients (carrying at least one mutation in ABCA4) were followed over 12 months with microperimetry using a Humphrey 10-2 test grid. Custom software was developed to automatically define and selectively follow the test points directly adjacent to dense scotoma points and to calculate their mean sensitivity (eMS). RESULTS: Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1. 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/yr) was significantly lower (β = -1.33, p < .001) than for eMS (2.9 ± 2.9 dB/yr). There was no difference in progression rates using automated vs manual grading (β = .09, p = .461). CONCLUSIONS: In Stargardt disease, 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 measure to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.
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. Here, we hypothesize that the functional decline is faster at the edge of the dense scotoma (eMS) than using overall MS. DESIGN: Multicenter, international, prospective cohort study: ProgStar study (NCT01977846). METHODS:Stargardt diseasepatients (carrying at least one mutation in ABCA4) were followed over 12 months with microperimetry using a Humphrey 10-2 test grid. Custom software was developed to automatically define and selectively follow the test points directly adjacent to dense scotoma points and to calculate their mean sensitivity (eMS). RESULTS: Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1. 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/yr) was significantly lower (β = -1.33, p < .001) than for eMS (2.9 ± 2.9 dB/yr). There was no difference in progression rates using automated vs manual grading (β = .09, p = .461). CONCLUSIONS: In Stargardt disease, 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 measure to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.
Authors: Etienne M Schönbach; Rupert W Strauss; Beatriz Muñoz; Yulia Wolfson; Mohamed A Ibrahim; David G Birch; Eberhart Zrenner; Janet S Sunness; Michael S Ip; SriniVas R Sadda; Sheila K West; Hendrik P N Scholl Journal: JAMA Ophthalmol Date: 2020-07-01 Impact factor: 7.389
Authors: Jason Charng; Tina M Lamey; Jennifer A Thompson; Terri L McLaren; Mary S Attia; Ian L McAllister; Ian J Constable; David A Mackey; John N De Roach; Fred K Chen Journal: Transl Vis Sci Technol Date: 2020-09-09 Impact factor: 3.283