The toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences, resembles that of prolonged continuous infusion. This finding, as well as the antitumor activity observed, supports wide phase II testing of DOX-SL in solid tumors.
Purpose To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). Design Prospective, double-masked, randomized clinical trial. Participants Patients with GA measuring from 1.25 to 18 mm2 based on spectral-domain optical coherence tomography imaging. Methods Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and lowluminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. Main Outcome Measures Change in area of GA at 26 weeks. Results Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55±0.94 and 2.02±0.74 mm in the eculizumab and placebo groups,respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19±0.12 and 0.18±0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37±0.22 mm in the eculizumab-treated eyes and by a mean of 0.37±0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. Conclusions Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the lowluminance deficit at baseline and the progression of GA over 6 months.Ophthalmology 2014;121:693-701 © 2014 by the American Academy of Ophthalmology.
Purpose-To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral-domain optical coherence tomography (SDOCT) fundus image. Design-Prospective longitudinal natural history studyParticipants-Eighty-six eyes of 64 patients with at least 6 months follow-up.Methods-Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SDOCT (Carl Zeiss Meditec, Dublin CA). The areas of GA identified on the SDOCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored.Main Outcome Measure-Enlargement rate of GA Results-At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59mm 2 (1.8 disc areas (DA)). The mean follow up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square-root scale (ICC=0.996). Inter-grader differences were not an important source of variability in lesion size measurement (ICC=0.999, 0.997). On average, the ER of GA per year was 1.2 mm 2 (0.47 DA; range [0.01 -3.61 mm 2 /year]. The ER correlated with the initial area of GA (r=0.45, p<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the enlargement rate (0.28 mm/yr) was not correlated with baseline size Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2012 April 1. r=-0.09,p=0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped facilitate sample size estimates for controlled clinical trials involving GA.Conclusions-The SDOCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium which should correlate with the loss of visual function.
Purpose To measure drusen area and volume in eyes with non-exudative age-related macular degeneration (AMD) using spectral domain optical coherence tomography imaging (SDOCT). Design Evaluation of diagnostic technology Participants One hundred three eyes from 74 patients with drusen Methods Patients with drusen secondary to non-exudative AMD were enrolled in this study. Five separate SDOCT scans, each consisting of 40000 uniformly spaced A-scans organized as 200 A-scans in each B-scan and 200 horizontal B-scans, were performed on each eye. Each scan covered a retinal area of 6×6 mm centered on the fovea. A novel algorithm was used to quantitatively assess drusen area and volume. Measurements from the entire scans, as well as in regions contained within 3 mm and 5 mm circles centered on the fovea, were analyzed. Test-retest standard deviations of drusen area and volume measurements were calculated for each eye. Main Outcome Measure Drusen area and volume Results The algorithm created drusen maps that permitted both qualitative and quantitative assessment of drusen area and volume. Both the qualitative appearance and the quantitative measurements of drusen area and volume were highly reproducible over the 5 different datasets. The intraclass correlation coefficient (ICC) was above 0.99 for both area and volume measurements on the entire dataset as well as the 3 mm and 5 mm circles. The correlation between lesion size and the test-retest standard deviations can be eliminated by performing a square-root transformation of the area measurements and a cube-root transformation of the volume measurements. These transformed data allowed for the inclusion of all drusen sizes in the calculation of an estimated single pooled test-retest standard deviation which will be useful for longitudinal studies of drusen natural history. Conclusions A novel algorithm for the qualitative and quantitative assessment of drusen imaged using SDOCT was shown to be highly reproducible. The ability to assess drusen volume reliably represents a new quantitative parameter to measure in AMD and may be useful when assessing disease progression, particularly in trials for treatments of non-exudative AMD.
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