Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study

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 PARTICIPANTSThis 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 MEASURESMean 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 RELEVANCEWe 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.

Peripheral Visual Fields in ABCA4 Stargardt Disease and Correlation With Disease Extent on Ultra-widefield Fundus Autofluorescence

“…31,33,34 Microperimetry has proven to be valuable in measuring macular function and in detecting disease progression in patients with STGD. 31,35–39 However, its utility is limited to the macular region. Although STGD universally starts in the macula, over time the disease progresses toward the periphery.…”

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1)

“…Microperimetry A scale of 0-20 dB served to determine the sensitivity for each test location. The term "deep scotoma" was defined for test locations with 0 dB (i.e., retinal locations where only the brightest stimulus was detected or no stimulus at all was detected), and the term "relative scotoma" for test locations with sensitivity better than 0 dB but less than 12 dB [16]. Mean sensitivity across all tested locations, and number of absolute and relative scotoma were calculated.…”

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

“…A scale from 0 to 20 dB served to determine the sensitivity for each test location. The term "deep scotoma" was defined for test locations with 0 dB (i.e., retinal locations where only the brightest stimulus was detected or no stimulus at all was detected), and the term "relative scotoma" for test locations with more than 0 dB but less than 12 dB [16]. Mean sensitivity across all tested locations and the number of absolute and relative scotomas were calculated.…”

“…P is the chosen probability for the SD that the BCEA is based on and the equation is solved for k [16][17][18]:…”