Review of Prolonged Monthly Therapy for DME
Although intravitreal (IVT) anti-VEGF therapy is used to treat numerous retinal conditions, controversy remains regarding its systemic safety. Thus, Avery and Gordon investigated the safety of IVT anti-VEGF in patients with diabetic macular edema, focusing on the subgroup of patients with the highest level of exposure: monthly injections for 2 years.
A search was conducted through MEDLINE, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and ophthalmology congress abstracts from Jan. 1, 1947 (the starting date of MEDLINE), to May 19, 2015. The researchers identified randomized clinical trials that evaluated patients who received monthly anti-VEGF injections for DME for 2 years and that included the outcome measures of cerebrovascular accidents (CVA), myocardial infarctions (MI), arteriothrombotic events, and mortality. The primary end points included CVA and all-cause mortality in the highest-dose arms. Secondary outcomes included MI, arteriothrombotic events, and vascular-related death.
Of 1,126 articles reviewed, 598 were removed as duplicate studies and 524 were excluded for lack of monthly treatment data for 2 years. This process left 4 studies that met criteria for the meta-analysis: 2 trials using monthly aflibercept and 2 using monthly ranibizumab, representing 1,328 study participants. The primary evaluation (1,078 subjects) combined the monthly aflibercept and the 0.5-mg ranibizumab arms and yielded an increased risk for death compared with sham and laser treatments (OR, 2.98; p = .003). Analysis including monthly aflibercept and 0.5-mg ranibizumab yielded an increased risk for CVA (OR, 2.33; p = .04) and vascular death (OR, 2.51; p = .03). No definitive increased risk for MI and arteriothrombotic events was seen with any dose combinations.
The authors concluded that for patients with DME, assessment of the highest-level exposure group revealed a possible increased risk for death and CVA. Consideration of total exposure to anti-VEGF agents when treating those at high risk for vascular disease may be important.
Detection of Strabismus by Lay Observers in Ethnically Diverse Images
Understanding the way that lay individuals perceive strabismus has implications for setting surgical goals and for counseling patients with strabismus. Chan et al. examined the magnitude at which strabismus is detectable by lay observers in an ethnically diverse set of images.
Photographs of 12 models (black, white, and Asian) were altered to simulate strabismus ranging from esotropia of 21 prism diopters (Δ) to exotropia of 21Δ. These images were presented to 120 individuals aged 21 years or older from the general community in Boston, who were asked whether strabismus was present. The researchers sought to determine the threshold angle at which 70% of lay observers detected the presence of strabismus.
In white and black models, the detection threshold was higher for esotropia than for exotropia (p < .001 for both). For white models, the threshold was 23.2Δ (95% CI, 21.0-26.5) for esotropia and 13.5Δ (95% CI, 12.5-14.6) for exotropia. For black models, the threshold was 20.8Δ (95% CI, 19.2-22.2) for esotropia and 16.3Δ (95% CI, 15.5-17.2) for exotropia. There was an opposite trend for the Asian models; the threshold for detecting esotropia (14.3Δ; 95% CI, 13.2-15.7) was lower than that for exotropia (20.9Δ; 95% CI, 18.0-24.6).
The authors concluded that esotropia was easier for lay observers to detect than exotropia in Asian models and that exotropia was easier to detect than esotropia in white and black models. This information may be of value when managing patients who have concerns about the social relevance of their strabismus. Future studies should include diverse individuals and make an effort to account for individual factors that may alter the perception of strabismus.
Oral Fluoroquinolones and Uveitis Risk
Oral fluoroquinolones are the most commonly prescribed antibiotic class in the outpatient setting, but recent reports have suggested an association between their use and an increased risk of uveitis. Sandhu et al. evaluated the hazard of uveitis in fluoroquinolone users by means of a retrospective cohort study conducted using medical claims data from a large national U.S. insurer.
Cohorts from ambulatory care centers across the United States were created including every new user of an oral fluoroquinolone or a β-lactam antibiotic prescription with at least 24 months of data prior to the date of the prescription from Jan. 1, 2000, to Jan. 30, 2013. Patients were excluded for any previous diagnosis of uveitis or a uveitis-associated systemic illness. Participants were censored for a new diagnosis of a uveitis-associated systemic illness, the end of an observation period, use of the other class of antibiotic, or removal from the insurance plan. The hazard of a uveitis diagnosis after a fluoroquinolone prescription was compared with that of a β-lactam prescription by means of multivariate regression with Cox proportional hazards models.
Of the 4,387,651 patients in the database, 843,854 receiving a fluoroquinolone and 3,543,797 receiving a β-lactam were included. After adjustment for age, race, and gender, no hazard was seen for developing uveitis at the 30-, 60-, or 90-day observation windows (hazard ratio [HR] range, 0.96-1.05; p > .38 for all comparisons). The 365-day observation period showed a small increase in the HR for the fluoroquinolone cohort (1.11; p < .001). Moxifloxacin produced an increased hazard for uveitis at every time point (HR range, 1.47-1.75; p < .001 for all comparisons). Secondary analysis demonstrated a similar hazard at 365 days for a later diagnosis of a uveitis-associated systemic illness after fluoroquinolone use (HR range, 1.46-1.96; p < .001 for all comparisons).
The authors concluded that these data do not support an association between oral fluoroquinolone use and uveitis. Instead, this study shows an association between oral fluoroquinolone use and the risk for uveitis-associated systemic illnesses, which is a possible source of bias that could explain the findings of previous studies.
JAMA Ophthalmology summaries are based on authors’ abstracts, as edited by senior editor(s).
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