Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. // Design: Multicenter, international, prospective cohort study. // Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. // Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. // Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality

Macular sensitivity measured with microperimetry in stargardt disease in the progression of atrophy secondary to stargardt disease (ProgStar) study report No. 7

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: Thiswas 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 lowMS ( < 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

A Workshop on Measuring the Progression of Atrophy Secondary to Stargardt Disease in the ProgStar Studies: Findings and Lessons Learned

The Progression of Atrophy Secondary to Stargardt Disease (ProgStar) studies were designed to measure the progression of Stargardt disease through the use of fundus autofluorescence imaging, optical coherence tomography, and microperimetry. The overarching objectives of the studies were to document the natural course of Stargardt disease and identify the most appropriate clinical outcome measures for clinical trials assessing the efficacy and safety of upcoming treatments for Stargardt disease. A workshop organized by the Foundation Fighting Blindness Clinical Research Institute was held on June 11, 2018, in Baltimore, MD, USA. Invited speakers discussed spectral-domain optical coherence tomography, fundus autofluorescence, and microperimetry methods and findings in the ProgStar prospective study. The workshop concluded with a panel discussion of optimal endpoints for measuring treatment efficacy in Stargardt disease. We summarize the workshop presentations in light of the most current literature on Stargardt disease and discuss potential clinical outcome measures and endpoints for future treatment trials