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Multicenter Study
. 2020 Jul 1;138(7):772-779.
doi: 10.1001/jamaophthalmol.2020.1735.

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13

Etienne M Schönbach  1   2 , Rupert W Strauss  1   3   4   5 , Beatriz Muñoz  1 , Yulia Wolfson  1 , Mohamed A Ibrahim  1   6 , David G Birch  7 , Eberhart Zrenner  8 , Janet S Sunness  9 , Michael S Ip  10   11 , SriniVas R Sadda  10   11 , Sheila K West  1 , Hendrik P N Scholl  1   12   13 ; ProgStar Study Group
Affiliations
Multicenter Study

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13

Etienne M Schönbach et al. JAMA Ophthalmol. .

Abstract

Importance: Functional end points for clinical trials investigating the efficacy of emerging treatments for Stargardt disease type 1 (STGD1) are needed.

Objective: To assess the yearly rate of change of macular function in patients with STGD1 using microperimetry.

Design, setting, and participants: This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. The study included participants with ABCA4-related STGD1 who were enrolled in the Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study at baseline. Data were analyzed from February 16, 2017, to December 1, 2019.

Exposure: ABCA4-related STGD1 with a minimum lesion size on fundus autofluorescence and a minimum visual acuity.

Main outcomes and measures: Changes in overall macular sensitivity (MS), deep scotoma count, number of points that tested normal, and location-specific sensitivity changes.

Results: Among the 359 eyes from 200 patients (87 [43.5%] men; mean [SD] age, 33.3 [15.2] years) who underwent microperimetry examination graded at baseline and month 12, the mean (SD) yearly change in MS was -0.68 (2.04) dB (95% CI, -0.89 to -0.47 dB; P < .001), and deep scotoma points increased by a mean (SD) of 1.56 (5.74) points per year. The points with sensitivity of 12 dB or higher decreased in sensitivity by a mean (SD) of -3.01 (9.84) dB (95% CI, -4.03 to -1.99 dB; P < .001). The mean (SD) yearly change in MS was not significantly different between the eyes with a grading of good or fair pattern placement at both visits (-0.67 [2.1] dB) and the eyes with a poor pattern placement during at least 1 visit (-0.64 [2.2] dB) (P = .91).

Conclusions and relevance: This study showed that MS and the number of deep scotoma points had measurably changed after follow-up of approximately 1 year. Microperimetry may serve as a useful functional outcome parameter for clinical trials aimed at slowing the progression of STGD1.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Schönbach reported receiving grants from the Leopoldina German Academy of Sciences and the Foundation Fighting Blindness during the conduct of the study. Dr Wolfson reported receiving grants from the Foundation Fighting Blindness Clinical Research Institute, the US Department of Defense, and the US Army Medical Research and Development Command Telemedicine and Advanced Technology Research Center during the conduct of the study. Dr Birch reported receiving personal fees from Applied Technologies Genetics Corporation, Nacuity Pharmaceuticals, the Foundation Fighting Blindness, and ProQR outside the submitted work. Dr Ip reported receiving personal fees from Boehringer Ingelheim, Thrombogenics, Quark, Omeros, Allergan, Amgen, Astellas, Alimera, Novartis, Genentech, Clearside, and Biogen outside the submitted work. Dr Sadda reported receiving personal fees and/or nonfinancial support from Heidelberg, Optos, Centervue, Roche/Genentech, Regeneron, Amgen, Novartis, 4DMT, Merck, Topcon, Nidek, and Carl Zeiss Meditec outside the submitted work. Dr West reported receiving grants from the Foundation Fighting Blindness during the conduct of the study. Dr Scholl reported receiving grants from the Swiss National Science Foundation, Wellcome Trust, the Foundation Fighting Blindness Clinical Research Institute, Novartis Pharma AG, and Pharma Research & Early Development of F. Hoffmann-La Roche Ltd and receiving personal fees from ReNeuron Group Plc/Ora Inc, Novo Nordisk, Boehringer Ingelheim Pharma GmbH & Co, Gerson Lehrman Group, and Guidepoint outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Enrollment and Outcomes
Among 444 eyes with MP-1 grading available at baseline and enrolled in the prospective ProgStar Study, a total of 359 eyes with a mean sensitivity grading available at both baseline and month 12 were included in the main analysis.
Figure 2.
Figure 2.. Outcome Measures for Microperimetry in Patients With Stargardt Disease
The Nidek MP-1 microperimeter was used to determine light sensitivity at each of 68 retinal locations of a modified Humphrey 10-2 test grid by iteratively adjusting the light intensity until the dimmest visible stimulus was found. Test locations with 0 dB (ie, sites seeing only the brightest stimulus or not seeing any stimuli) were defined as deep scotomas (DS), and test locations with more than 0 dB but less than 12 dB were defined as relative scotomas. In the example of a left eye of a patient with ABCA4-related Stargardt disease who underwent 3 examinations every 6 months, the mean sensitivity in decibels (mean of all 68 sensitivity values) is displayed in the top left corner and the number of DS is shown in the top right corner.
Figure 3.
Figure 3.. Location-Specific Outcome Measures for Microperimetry in Patients With Stargardt Disease
For this analysis, we required use of the follow-up function and good or fair pattern placement on both study visits, reducing the number of included eyes to 106. The test grid was divided into 3 regions: the central or foveal 4 points that were 1.7° away from the center of the grid (red overlay), the 12 perifoveal points were at a distance of 3.5° to 4.7° away and were grouped as the inner ring (yellow overlay), and the remainder of the test locations 5.6° to 10.1° from the grid center were grouped as the outer ring (light blue overlay). The numbers show the count of deep scotomas (DS) and the mean sensitivity of all test locations. All measurements are indicated in decibels (red for the mean sensitivity in the foveal region, yellow for the inner ring, and light blue for the outer ring).
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References

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