Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7

Abstract

Importance: New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity.

Objective: To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry).

Design, setting, and participants: This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal," "relative," or "deep" scotoma.

Main outcomes and measures: Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas.

Results: Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P < .001). Longer duration of STGD1 was associated with worse MS (β = -0.18; P < .001), with a lower number of normal test points (β = -0.71; P < .001), and with a higher number of deep scotoma points (β = -0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent).

Conclusions and relevance: We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Scholl is a paid consultant of the following entities: Astellas Institute for Regenerative Medicine; Boehringer Ingelheim Pharma GmbH and Co KG; Daiichi Sankyo Inc; Gerson Lehrman Group; Guidepoint; and Shire. Dr Scholl is member of the Scientific Advisory Board of Gensight Biologics; Vision Medicines Inc; and Intellia Therapeutics Inc. Dr Scholl is member of the Data Monitoring and Safety Board/Committee of the following entities: Genentech Inc/F. Hoffmann-La Roche Ltd; Genzyme Corp/Sanofi, and ReNeuron Group Plc/Ora Inc. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Johns Hopkins University and Bayer Pharma AG have an active research collaboration and option agreement. These arrangements have also been reviewed and approved by the University of Basel in accordance with its conflict of interest policies. Dr Hendrik Scholl is principal investigator of grants at the University of Basel sponsored by the following entities: Acucela Inc; NightstaRx Ltd; and QLT Inc. Grants at University of Basel are negotiated and administered by the institution, which receives them on its proper accounts. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the project(s). Dr Sheila West is a scientific technical advisory committee member for the Alcon Research Institute and for Research to Prevent Blindness. Dr Yulia Wolfson is an employee for Optovue Inc. No other disclosures were reported.

Figures

Figure 1.. Enrollment and Outcomes

Among 489 eyes enrolled in the prospective ProgStar Study, a total of 326 were included in the sensitivity analysis of the macula and 322 eyes were included in the analysis of mean sensitivity.

Figure 2.. Microperimetric Sensitivity and Demographics

Scatterplots showing the correlation between microperimetric sensitivity with the duration of Stargardt disease (STGD1), the age at onset of STGD1, and the duration of STGD1 symptoms. Univariate linear regression analyses.

Figure 3.. Case of Discrepancy Between Microperimetric Sensitivity and Visual Acuity

The right eye of a 35-year-old man with mean sensitivity of 0.12 dB and best-corrected visual acuity of 77 Early Treatment Diabetic Retinopathy Study letter score (about 20/32 Snellen equivalent). Fixation was within an island of nonatrophic retina on a coregistered fundus autofluorescence image.