Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Correlation of Aging and Segmental Choroidal Thickness Measurement using Swept Source Optical Coherence Tomography in Healthy Eyes.

To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattler's (CS) layer and/or the large vessel layer in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm.We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan.Total choroidal thicknesses at each of the five sites were related to subject age (P<0.0001). The choroid was thinnest at the nasal site, followed by the temporal, inferior, superior and finally the subfoveal site itself. The total choroidal thickness at the nasal site was significantly less than those at the other four sites (p<0.05). The CS layer showed thinning which correlated with age (P<0.0001). The thickness of the choroidal large vessel layer also decreased with age (p = 0.02). Subfoveal choroidal thickness was calculated as follows: 443.89-2.98×age (μm) (P<0.0001).Subfoveal choroidal thickness decreases by 2.98 μm each year. Total choroidal thickness diminishes with age. The CS and large vessel layers of the choroid at the subfovea showed significant decreases, though only the former correlated strongly with age

Morphological Changes and Prognostic Factors before and after Photodynamic Therapy for Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease of unknown etiology, but half-dose photodynamic therapy (hPDT) is well known to be effective for CSC. Infrared reflectance (IR) has been shown to be effective for detecting retinal pigmented epithelial and choroidal lesions, but no reports have focused on chorioretinal changes using IR images after as compared to before hPDT. This study aimed to clarify the features of IR images as well as retinal and choroidal morphological changes before and after treatment with verteporfin hPDT for CSC. We also examined prognostic factors associated with CSC treatment. This was a retrospective study that included 140 eyes of 140 patients (male/female ratio 122:18, mean age 53.4 ± 10.8 years) diagnosed with CSC who underwent hPDT in our hospital during the period from April 2015 to December 2018. We determined changes in visual acuity, therapeutic efficacy, central retinal thickness (CRT), central choroidal thickness (CCT), and IR images at one and three months after hPDT as compared to before treatment. Dry macula was defined as a complete resolution of serous retinal detachment after hPDT. History of smoking, disease duration, presence of drusen, presence of retinal pigment epithelium abnormalities, type of fluorescein angiographic leakage, and presence of choroidal vascular hyperpermeability were investigated as prognostic factors associated with treatment efficacy. CRT and CCT were measured using optical coherence tomography (Spectralis HRA-2; Heidelberg Engineering), and IR images after versus before treatment were compared using ImageJ software (version 1.52) to calculate the mean luminance for a 3 × 3 mm area in the macula. Compared with the values before treatment, CCT, CRT, and visual acuity showed significant improvements at one and three months after treatment, and the mean luminance of IR images was also significantly increased. Furthermore, the luminance on IR images tended to rise, though the values at one month and three months after treatment did not differ significantly. Disease duration was significantly associated with dry macula one month after treatment, and visual acuity and CRT before hPDT were both significantly related to dry macula three months after treatment. IR images tended to improve over time, from before treatment through one and three months after hPDT

Mean choroidal thicknesses at each of the five sites.

<p>Mean choroidal thicknesses at each of the five sites.</p

Correlations among the mean choroidal thicknesses of the five sites.

<p>Correlations among the mean choroidal thicknesses of the five sites.</p

Subfoveal large vessel layer thickness.

<p>Scatterplot for age and subfoveal large vessel layer choroidal thickness measured at a single point are presented. There is a negative correlation between age and the choroidal thickness of the large vessel layer (p = 0.0209, y = 250.07–0.87×age. R² = 0.056).</p