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Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF 8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF 8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm 3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p<0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF 8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019).
RESUMO
OBJECTIVE: The purpose of this study was to evaluate the pupil response to chromatic stimuli in patients with lesions in the dorsal midbrain and possibly gain new insights into the afferent pupillary pathways. METHODS: Color pupillography was performed in 5 patients with dorsal midbrain syndrome (DMS), and their results were compared with those of 20 healthy control subjects. We used full-field red stimuli (605 nm) that primarily address the rod/cone system and blue stimuli (420 nm) that preferentially activate intrinsically photosensitive retinal ganglion cells (ipRGCs) directly, with a duration of 4 seconds and a stimulus intensity of 28 lx corneal illumination under mesopic conditions. One eye was stimulated, and the consensual pupil response was recorded and analyzed. RESULTS: The pupillary light reflex in patients with DMS was reduced, differed in shape, and showed a prolonged latency time compared to normal subjects. The blue response was less affected than the red response: the mean maximal relative amplitude (M) was 15.8% (SD = 7.8) in patients with DMS compared with 43.0% (SD = 5.5) in normal subjects for red stimulation, and M = 40.8%, SD = 8.4 (DMS) with M = 58.3%, SD = 4.8 (normals) for blue stimulation. The reduction was 63% for red stimulation but only 30% for blue stimulation in patients with DMS. Moreover, there was a preserved postillumination pupil response to blue stimulation in DMS patients. CONCLUSIONS: In DMS, the melanopsin-mediated ipRGC pathway appeared relatively preserved.
