Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study.

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety and effectiveness of VN. Here, we present the outcomes of 103 patients treated with VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female, and the mean (SD) duration of the follow up was 0.8 (0.64) years (maximum: 2.3 years). Thirty-five patients (34%) experienced ocular treatment-emergent adverse events (TEAEs), most frequently related to chorioretinal atrophy (n = 13 [12.6%]). Eighteen patients (17.5%; 24 eyes [13.1%]) experienced ocular TEAEs of special interest, including intraocular inflammation and/or infection related to the procedure (n = 7). The mean (SD) changes from baseline in full-field light-sensitivity threshold testing (white light) at month 1, month 6, year 1, and year 2 were -16.59 (13.48) dB (51 eyes), -18.24 (14.62) dB (42 eyes), -15.84 (14.10) dB (10 eyes), and -13.67 (22.62) dB (13 eyes), respectively. The change in visual acuity from baseline was not clinically significant. Overall, the outcomes of the PERCEIVE study are consistent with the findings of VN pivotal clinical trials.

Efficacy and safety of ranibizumab 0.5 mg in Chinese patients with visual impairment due to diabetic macular edema: results from the 12-month REFINE study.

PURPOSE: To demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic macular edema (DME). METHODS: REFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed. RESULTS: Ranibizumab was statistically superior (p < 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals. CONCLUSION: Ranibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months.

Light visor treatment for jet lag after westward travel across six time zones.

INTRODUCTION: The aim of this field study was to evaluate the efficacy of a light treatment for jet lag, using a head-mounted light visor, following a westward flight across six time zones. METHODS: There were 20 subjects who were exposed to bright white light (3000 lux) or dim red light (10 lux) for 3 h on the first two evenings after a flight from Zurich to New York. Salivary dim light melatonin onset (DLMO), assessed 2 d before and 2 d after the flight, provided a measure of circadian phase. Sleep was recorded by actigraphy, while post-flight performance testing and subjective scales provided additional indices of jet lag severity. RESULTS: The DLMO measurements showed a larger phase delay in the bright light than in the dim light group (2.59 h vs. 1.58 h, p < 0.02). There was no overall difference in sleep efficiency (SE) between the two groups, but a significant Group x Night interaction reflected a small increase across the first two post-flight nights in the bright light group, and a small decrease in the dim light group. Reaction time on one of two performance tests was consistently faster in the dim light group, but was unrelated to circadian phase or to prior sleep. There were no major group differences in subjective sleep quality, daytime sleepiness, jet lag severity, or mood. DISCUSSION: This is the first full-scale study to show that bright light treatment can accelerate circadian reentrainment following transmeridian travel. However, the effect on reentrainment rate was modest, and was not accompanied by any improvement in sleep, performance, or subjective assessments of jet lag symptoms.

Failure of timed bright light exposure to alleviate age-related sleep maintenance insomnia.

OBJECTIVES: To determine whether a twice-weekly maintenance schedule of evening bright light exposure is effective in alleviating sleep maintenance insomnia on a long-term basis, after the establishment of a more favorable phase relationship between the core body temperature (CBT) rhythm and sleep. DESIGN: Subjects underwent light treatment while living at home. Eleven to 13 consecutive days of acute light treatment (active) were followed by a 3-month maintenance light treatment period (active or control). Subjects completed five laboratory sessions: before and after the acute phase and once a month during the maintenance period. SETTING: Sleep laboratory and subjects' homes. PARTICIPANTS: Fifteen older subjects (seven women, eight men; aged 63-84) with chronic (>1 year) complaints of sleep maintenance insomnia. INTERVENTIONS: During the acute phase, all participants were exposed to evening bright light (approximately 9:00 p.m. to 11:00 p.m.;>4,000 lux). During the maintenance phase, light treatment was reduced to a twice-weekly schedule, in which the active group received bright light from approximately 9:00 p.m. to 11:00 p.m. and the control group received bright light from 3:00 p.m. to 5:00 p.m. MEASUREMENTS: During each laboratory session, polysomnographic sleep and CBT were measured. RESULTS: Bright light exposure during the acute treatment resulted in an average phase delay in the temperature rhythm (Tmin) of 94 minutes. Sleep quality was not improved. No significant differences between active and control subjects were found during the maintenance phase; in both groups, Tmin gradually reverted to the baseline phase position, and sleep efficiency remained unchanged. CONCLUSIONS: Although a significant phase shift in CBT was achieved during the acute treatment phase, no improvement in sleep quality was observed. Twice-weekly light exposure was not effective in maintaining the circadian phase shift over the subsequent 3 months. Issues of compliance and alternate etiologies for the sleep maintenance insomnia are discussed.