Maryann Redford

Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: Two-Year Results

OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. DESIGN Multicenter, randomized clinical trial. PARTICIPANTS Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. INTERVENTIONS At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. MAIN OUTCOME MEASURES Mean change in visual acuity. RESULTS Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

The prevalence of oral lesions was assessed in a five-center subset of the Womens Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposis sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

Randomized clinical trial of treatments for symptomatic convergence insufficiency in children

OBJECTIVE To compare home-based pencil push-ups (HBPP), home-based computer vergence/accommodative therapy and pencil push-ups (HBCVAT+), office-based vergence/accommodative therapy with home reinforcement (OBVAT), and office-based placebo therapy with home reinforcement (OBPT) as treatments for symptomatic convergence insufficiency. METHODS In a randomized clinical trial, 221 children aged 9 to 17 years with symptomatic convergence insufficiency were assigned to 1 of 4 treatments. MAIN OUTCOME MEASURES Convergence Insufficiency Symptom Survey score after 12 weeks of treatment. Secondary outcomes were near point of convergence and positive fusional vergence at near. RESULTS After 12 weeks of treatment, the OBVAT groups mean Convergence Insufficiency Symptom Survey score (15.1) was statistically significantly lower than those of 21.3, 24.7, and 21.9 in the HBCVAT+, HBPP, and OBPT groups, respectively (P < .001). The OBVAT group also demonstrated a significantly improved near point of convergence and positive fusional vergence at near compared with the other groups (P <or= .005 for all comparisons). A successful or improved outcome was found in 73%, 43%, 33%, and 35% of patients in the OBVAT, HBPP, HBCVAT+, and OBPT groups, respectively. CONCLUSIONS Twelve weeks of OBVAT results in a significantly greater improvement in symptoms and clinical measures of near point of convergence and positive fusional vergence and a greater percentage of patients reaching the predetermined criteria of success compared with HBPP, HBCVAT+, and OBPT. Application to Clinical Practice Office-based vergence accommodative therapy is an effective treatment for children with symptomatic convergence insufficiency. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00338611.

Validity of the convergence insufficiency symptom survey: a confirmatory study.

Purpose. The objectives of the present study were to evaluate whether investigator bias influenced the Convergence Insufficiency Symptom Survey (CISS) scores of children with normal binocular vision (NBV) in our original validation study, reevaluate the usefulness of the cutoff score of 16, and reexamine the validity of the CISS. Methods. Six clinical sites participating in the Convergence Insufficiency Treatment Trial (CITT) enrolled 46 children 9 to <18 years with NBV. Examiners masked to the child’s binocular vision status administered the CISS. The mean CISS score was compared with that from the children with NBV in the original, unmasked CISS study and also to that of the 221 symptomatic convergence insufficiency (CI) children enrolled in the CITT. Results. The mean (±standard deviation) CISS score for 46 subjects with NBV was 10.4 (±8.1). This was comparable with our prior unmasked NBV study (mean = 8.1 (±6.2); p = 0.11) but was significantly different from that of the CITT CI group (mean = 29.8 ± 9.0; p < 0.001). Eighty-three percent of these NBV subjects scored <16 on the CISS, which is not statistically different from the 87.5% found in the original unmasked study (p = 0.49). Conclusions. Examiner bias did not affect the CISS scores for subjects with NBV in our prior study. The CISS continues to be a valid instrument for quantifying symptoms in 9 to <18-year-old children. These results also confirm the validity of a cut-point of ≥16 in distinguishing children with symptomatic CI from those with NBV.

Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration

OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. DESIGN Multicenter, randomized clinical trial. PARTICIPANTS Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. INTERVENTIONS At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. MAIN OUTCOME MEASURES Mean change in visual acuity. RESULTS Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Systemic and mucosal differences in HIV burden, immune, and therapeutic responses.

Background:Mucosal tissues represent major targets for HIV transmission but differ in susceptibility and reservoir function by unknown mechanisms. Methods:In a cross-sectional study, HIV RNA and infectious virus were compared between oral and genital compartments and blood in HIV-infected women, in association with clinical parameters, copathogens, and putative innate and adaptive HIV inhibitors. Results:HIV RNA was detectable in 24.5% of women from all 3 compartments, whereas 45% had RNA in only 1 or 2 sites. By comparison, infectious HIV, present in blood of the majority, was rare in mucosal sites. Innate mediators, secretory leukocyte protease inhibitor and thrombospondin, were highest in mucosae. Highly active antiretroviral therapy was associated with an 80% decreased probability of shedding. Multivariate logistic regression models revealed that mucosal HIV RNA was associated with higher plasma RNA, infectious virus, and total mucosal IgA, but not IgG. There was a 37-fold increased probability of detecting RNA in both genital and oral specimens (P = 0.008; P = 0.02, respectively) among women in highest versus lowest IgA tertiles. Conclusions:Mucosal sites exhibit distinct characteristics of infectious HIV, viral shedding, and responses to therapy, dependent upon both systemic and local factors. Of the putative innate and adaptive mucosal defense factors examined, only IgA was associated with HIV RNA shedding. However, rather than being protective, there was a striking increase in probability of detectable HIV RNA shedding in women with highest total IgA.

Visual Function of Moderately Hyperopic 4- and 5-Year-Old Children in the Vision in Preschoolers - Hyperopia in Preschoolers Study.

PURPOSE To compare visual performance between emmetropic and uncorrected moderately hyperopic preschool-age children without strabismus or amblyopia. DESIGN Cross-sectional study. METHODS setting: Multicenter, institutional. patient or study population: Children aged 4 or 5 years. intervention or observation procedures: Visual functions were classified as normal or reduced for each child based on the 95% confidence interval for emmetropic individuals. Hyperopic (≥3.0 diopters [D] to ≤6.0 D in the most hyperopic meridian; astigmatism ≤1.50 D; anisometropia ≤1.0 D) and emmetropic status were determined by cycloplegic autorefraction. MAIN OUTCOME MEASURES Uncorrected monocular distance and binocular near visual acuity (VA); accommodative response; and near random dot stereoacuity. RESULTS Mean (± standard deviation) logMAR distance visual acuity (VA) among 248 emmetropic children was better than among 244 hyperopic children for the better (0.05 ± 0.10 vs 0.14 ± 0.11, P < .001) and worse eyes (0.10 ± 0.11 vs 0.19 ± 0.10, P < .001). Mean binocular logMAR near VA was better in emmetropic than in hyperopic children (0.13 ± 0.11 vs 0.21 ± 0.11, P < .001). Mean accommodative response for emmetropic children was lower than for hyperopic subjects for both Monocular Estimation Method (1.03 ± 0.51 D vs 2.03 ± 1.03 D, P < .001) and Grand Seiko (0.46 ± 0.45 D vs 0.99 ± 1.0 D, P < .001). Median near stereoacuity was better in emmetropic than in than hyperopic children (40 sec arc vs 120 sec arc, P < .001). The average number of reduced visual functions was lower in emmetropic than in hyperopic children (0.19 vs 1.0, P < .001). CONCLUSIONS VA, accommodative response, and stereoacuity were significantly reduced in moderate uncorrected hyperopic preschool children compared to emmetropic subjects. Those with higher hyperopia (≥4 D to ≤6 D) were at greatest risk, although more than half of children with lower magnitudes (≥3 D to <4 D) demonstrated 1 or more reductions in function.

Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration: 2-Year Results: Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group‡*

OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. DESIGN Multicenter, randomized clinical trial. PARTICIPANTS Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. INTERVENTIONS At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. MAIN OUTCOME MEASURES Mean change in visual acuity. RESULTS Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.