Risk of MI and Stroke With Intravitreal Bevacizumab in AMD
Concerns have been raised about whether intravitreal VEGF inhibitors increase the risk of myocardial infarction (MI) and stroke, but the peer-reviewed literature presents conflicting opinions. This prompted Etminan et al. to undertake a population-based study to examine the risk in patients receiving bevacizumab for age-related macular degeneration (AMD). They found that intravitreal bevacizumab did not appear to increase these cardiovascular events.
The authors used 2 cohorts of AMD patients in British Columbia, Canada, and 2 study designs: First, in a retrospective cohort study, they examined the risk of MI and stroke in patients with wet AMD who received intravitreal bevacizumab compared with those not taking VEGF inhibitors. Second, they conducted a nested case-control study among new users of intravitreal bevacizumab on the risk of MI or stroke. In both studies, a number of adjustments were applied in the analyses, including age, sex, presence of diabetes and vascular disorders, and the use of various drugs.
The retrospective cohort study included 5,644 patients who received bevacizumab and 2,564 who did not receive any anti-VEGF agent; all participants had been diagnosed with wet AMD. The rate of MI among intravitreal bevacizumab users was 11/1,000 person-years compared with 14.9/1,000 person-years in nonusers, yielding an adjusted rate ratio (RR) for MI of 0.70 (95% CI, 0.50-1.00).
The nested case-control study included 313 cases of MI with 3,130 matched controls as well as 65 cases of stroke matched with 650 corresponding controls. Several analyses were performed to investigate a possible dose-response, but no significant increase in the risk of either MI or stroke was found with either single or multiple injections of bevacizumab.
The authors concluded that, given the comparable effectiveness of bevacizumab and ranibizumab, these results will be reassuring to clinicians who choose to use off-label bevacizumab as a more cost-effective anti-VEGF therapy for their patients.
A PCR-Based Algorithm to Detect and Prevent Adenoviral Conjunctivitis Transmission
Adenoviral conjunctivitis (AVC) can range from a mild, self-limited condition to prolonged ocular morbidity in the case of epidemic keratoconjunctivitis (EKC). At presentation, it is difficult to distinguish mild AVC from EKC or even from other causes of red eye. Kuo et al. reported the 36-month results of a pilot program at Johns Hopkins Hospital (JHH) to reduce the transmission of EKC in the workplace through polymerase chain reaction (PCR) confirmation of adenovirus and a defined furlough protocol.
For employees with suspected conjunctivitis, the JHH algorithm consists of initial evaluation by nurse practitioners in the Occupational Health clinic who were trained by corneal specialists to recognize signs or symptoms consistent with AVC and to collect swab specimens from the inferior fornix. These swabs are submitted to a JHH laboratory for PCR testing. Employees with suspected viral conjunctivitis are evaluated, swabbed, and discharged home within 30 minutes of intake. Results from specimens received by 3 p.m. are available the next morning.
Employees whose swabs are positive for AVC are given a 14-day work furlough, while those whose swabs are negative return to work when free of signs and symptoms (generally 1-3 days after onset). Employees in both groups must be cleared by an Occupational Health nurse practitioner before returning to work.
Between Nov. 22, 2011, and Oct. 31, 2014, 858 of 4,883 initial employee Occupational Health visits (18%) were due to eye-related complaints. The nurse practitioners judged 542 (62%) of the eye complaints as possible AVC cases and submitted swabs for PCR; 44 of these were confirmed positive for AVC, and the employees were given a 14-day furlough. Specific adenoviral serotypes could be determined in 32 of the 44, and 13 of these had serotypes associated with the more serious EKC.
The authors noted that outbreaks reported in hospitals and eye clinics have caused substantial morbidity and lost productivity. However, since implementation of this pilot program at JHH, no health care–associated AVC outbreaks have occurred, and substantially fewer employees were placed on furlough than would have been the case had clinical diagnosis alone been used.
Thus, the authors concluded that implementation of this algorithm, encompassing rapid detection of AVC and isolation of affected employees, has been successful and cost-effective for their institution. They noted that no PCR test for the detection of adenovirus in conjunctival specimens is commercially available, so clinical laboratories must develop their own tests. They also stated that further study and refinement of serotyping may reveal that shorter furloughs may be appropriate in some cases.
Predictors of Response to Anti-VEGF Treatment of AMD
Despite the overall success of anti-VEGF medication in treating age-related macular degeneration (AMD), response to these drugs—in both visual and anatomic outcomes—varies among individual patients. Shah et al. conducted a retrospective chart review to assess behavioral, demographic, and, especially, genetic factors that contribute to these differences.
This study included 72 AMD patients treated at a single institution. Best-corrected visual acuity (BCVA) and central foveal thickness data were collected at baseline, 6 months, and 12 months. Demographic and behavioral variables analyzed were age, sex, body mass index (BMI), education, and smoking history. Genetic factors studied included a wide variety of genes and alleles involved with complement, angiogenesis, lipid, immune/inflammatory response, and extracellular matrix pathways. Two loci in complement factor H (CFH) were included in a risk score to determine the association between CFH risk and improvement in VA and foveal thickness. The researchers also examined associations between a previously developed risk score for progression to advanced AMD that incorporated demographic, behavioral, and genetic factors.
The researchers found a small but not statistically significant improvement in VA in the overall study population following anti-VEGF treatment (mean: 3.7 ± 3.0 letters). In terms of specific factors studied, significantimprovement in VA was observed for the nonrisk CFH Y402H genotype (p < .001) and for a low CFH risk score (p = .019). Improvement in central foveal thickness was observed in all genotype groups, but it was significantly better in the low CFH risk score group (p = .033). A significant improvement in mean VA was observed for smokers (p < .001), but this relationship was not seen for central foveal thickness. No other behavioral or demographic variables were significant. The authors pointed out that there was no association between the AMD composite risk score and treatment response, implying that the factors leading to development of advanced AMD are not necessarily the same as those affecting treatment response.
American Journal of Ophthalmology summaries are written by Peggy Denny and edited by Richard K. Parrish II, MD.
More from this month’s Journal Highlights