Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study ...designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC.
Medically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it.
One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively.
The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
IMPORTANCE Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. ...OBJECTIVE To describe 10-year progression rates to intermediate or advanced AMD. DESIGN, SETTING, AND PARTICIPANTS We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years. EXPOSURE Treatment with antioxidant vitamins and minerals. MAIN OUTCOMES AND MEASURES Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits. RESULTS The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200. CONCLUSIONS AND RELEVANCE The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.
Prevalence of Visual Impairment in the United States Vitale, Susan; Cotch, Mary Frances; Sperduto, Robert D
JAMA : the journal of the American Medical Association,
05/2006, Letnik:
295, Številka:
18
Journal Article
Recenzirano
CONTEXT The prevalence of visual impairment in the US public has not been surveyed nationally in several decades. OBJECTIVE To estimate the number of US individuals aged 12 years or older who have ...impaired distance vision due to uncorrected refractive error. DESIGN, SETTING, AND PARTICIPANTS The National Health and Nutrition Examination Survey (NHANES), using a multistage probability sampling design, included a vision evaluation in a mobile examination center. Visual acuity data were obtained from 13 265 of 14 203 participants (93.4%) who visited the mobile examination center in 1999-2002. Visual impairment was defined as presenting distance visual acuity of 20/50 or worse in the better-seeing eye. Visual impairment due to uncorrected refractive error was defined as (presenting) visual impairment that improved, aided by automated refraction results, to 20/40 or better in the better-seeing eye. MAIN OUTCOME MEASURES Presenting distance visual acuity (measured with usual corrective lenses, if any) and distance visual acuity after automated refraction. RESULTS Overall, 1190 study participants had visual impairment (weighted prevalence, 6.4%; 95% confidence interval CI, 6.0%-6.8%), and of these, 83.3% could achieve good visual acuity with correction (95% CI, 80.9%-85.8%). Extrapolating these findings to the general US population, approximately 14 million individuals aged 12 years or older have visual impairment (defined as distance visual acuity of 20/50 or worse), and of these, more than 11 million individuals could have their vision improved to 20/40 or better with refractive correction. CONCLUSIONS Visual impairment due to uncorrected refractive error is a common condition in the United States. Providing appropriate refractive correction to those individuals whose vision can be improved is an important public health endeavor with implications for safety and quality of life.
To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration ...(AMD).
Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study.
We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study.
Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses.
Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular NV or central geographic atrophy CGA), and moderate visual acuity loss from baseline (≥15 letters).
Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio OR, 0.66, 95% confidence interval CI, 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases.
Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
IMPORTANCE The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The ...Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURES Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00345176
To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study ...(AREDS).
Clinic-based prospective cohort study.
Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract.
Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery.
Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs.
A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery.
These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery.
Cohort study.
Four thousand five hundred seventy-seven participants (8050 eyes) from a ...multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS).
Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately.
Neovascular AMD, GA, and central GA (CGA; involving the center of the macula).
The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval CI, 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA.
The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
BACKGROUND: ω-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing ...age-related macular degeneration (AMD). OBJECTIVE: We investigated whether ω-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD. DESIGN: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on ω-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit. RESULTS: Participants who reported the highest ω-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P less-than or equal to 0.02) and 0.68 (95% CI: 0.49, 0.94; P less-than or equal to 0.02). CONCLUSIONS: The 12-y incidence of CGA and NV AMD in participants at moderate-to-high risk of these outcomes was lowest for those reporting the highest consumption of ω-3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.
PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District, northeast of Beijing, the Peoples Republic of China.
METHODS: Random selection ...of village-based clusters was used to identify a sample of children 5 to 15 years of age. Resident registration books were used to enumerate eligible children in the selected villages and identify their current school. Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998, including visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus. Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools.
RESULTS: A total of 6,134 children from 4,338 households were enumerated, and 5,884 children (95.9%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 12.8%, 10.9%, and 1.8%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 89.5% of the 1,236 eyes with reduced vision, amblyopia in 5%, other causes in 1.5%, with unexplained causes in the remaining 4%. Myopia −0.5 diopter or less in either eye was essentially absent in 5-year-old children, but increased to 36.7% in males and 55.0% in females by age 15. Over this same age range, hyperopia 2 diopters or greater decreased from 8.8% in males and 19.6% in females to less than 2% in both. Females had a significantly higher risk of both myopia and hyperopia.
CONCLUSIONS: Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District. More than 9% of children could benefit from prescription glasses. Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts.
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