1-Year Efficacy of 3 Anti-VEGF Agents in DME
Wells et al., on behalf of the Diabetic Retinopathy Clinical Research Network, reported additional outcomes from a randomized trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST). The authors used a post hoc exploratory analysis of data from that trial in a group of 660 adults with DME and decreased VA.
Treatment involved repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. Prespecified subgroups were established according to baseline VA and CST. For VA, the thresholds were defined as worse (20/50 or worse) or better (20/32-20/40) VA; for CST, they were defined as thicker (≥400 μm) or thinner (250-399 μm).
In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes were similar between groups; mean change was +7.2, +8.4, and +7.6 letters for aflibercept, bevacizumab, and ranibizumab, respectively.
However, results from the subgroup with better VA and thicker CST at baseline (31-43 eyes) suggested worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively; and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17%-60%) for aflibercept vs. bevacizumab, 25% (5%-46%) for ranibizumab vs. bevacizumab, and 13% (–8% to 35%) for aflibercept vs. ranibizumab.
These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, the authors recommended caution in using the data to guide treatment decisions.
Prior Insulin Therapy and Visual Function Outcomes in Diabetes
Interventions to improve glycemic control through early intensive treatment of diabetes have been shown to reduce rates of severe retinopathy and preserve visual acuity (VA). Gubitosi-Klug et al., on behalf of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) studies, assessed the effects of prior intensive insulin treatment and risk factors on patient-reported visual function in this DCCT/EDIC cohort.
The cohort included 1,184 participants with type 1 diabetes from the DCCT/EDIC studies (randomized clinical trial/observational follow-up study) who completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) during EDIC years 17 through 20 (Sept. 1, 2009, through April 30, 2014) at 28 institutions across the United States and Canada. The primary outcome was the composite NEI-VFQ-25 score. Secondary outcomes were VA, retinopathy level (determined from stereoscopic color fundus photographs), and NEI-VFQ-25 subscale scores. The composite NEI-VFQ-25 scale and its subscales were scored 0 to 100, corresponding to poor to excellent function, respectively.
The overall average NEI-VFQ-25 score for the 1,184 participants (mean [SD] age, 52.3 [6.9] years; 48% female) with a 30-year duration of diabetes was high: median, 91.7, with an interquartile range (IQR) of 89.7-96.9. For the intensive treatment group (n = 605), the median score was 94.7, and IQR was 91.0-97.2. The conventional treatment group (n = 579) had a median of 94.0 and an IQR of 88.4-96.1 (p = .006 for intensive vs. conventional).
After adjustment for sex, age, hemoglobin A1c level, and retinopathy level at DCCT baseline, the former intensive treatment group had a significant, albeit modest, improvement in overall NEI-VFQ-25 score compared with the former conventional diabetes treatment group (median difference, −1.0; 95% CI, −1.7 to −0.3; p = .006). This beneficial treatment effect was fully attributed to the prior glycemic control in DCCT.
Those with VA worse than 20/100 reported the largest decline in visual function (median difference, −21.0; 95% CI, −40.5 to −1.6; p = .03). The study suggests that intensive diabetes therapy modestly improved NEI-VFQ-25 scores 30 years after the start of the DCCT. Among all factors contributing to patient-reported visual function, VA had the greatest effect.
Concentration Accuracy of Compounded Mitomycin C
Because ophthalmologists rely on accurate concentrations of mitomycin C (MMC) to prevent scarring with trabeculectomy surgery, Kinast et al. studied whether the measured concentration differs from the expected concentration of 0.4 mg/mL of MMC for ophthalmic surgery. Their analysis revealed a wide range above and below that standard.
In this laboratory investigation conducted in July 2013, the authors acquired 60 samples of 0.4 mg/mL of MMC that were prepared using a spectrum of common compounding and storage techniques (refrigeration, freezing, and immediately compounded dry powder) from various types of pharmacies (an academic hospital, a community hospital, and an independent accredited compounding pharmacy).
The investigators obtained pure powdered MMC to generate calibration curves and sulfanilamide as an internal standard. They used C18 reversed-phase high-performance liquid chromatography (HPLC) to measure the MMC concentration of all samples. The HPLC method for measuring MMC demonstrated acceptable accuracy (92%-100%), precision (2%-6% coefficient of variation), and linearity (mean correlation coefficient of r2 = 0.99).
Using this HPLC method, the researchers found that measured MMC concentration was 12.5% lower than the expected 0.4 mg/mL value (mean [SD], 0.35 [0.04] mg/mL; 95% CI, 0.34-0.36; p < .001), with concentrations ranging from 0.26 to 0.46 mg/mL.
The authors concluded that common compounding and storage techniques for MMC resulted in a lower accuracy and wider range of concentration than expected. In particular, the frozen samples exhibited the lowest concentration values and widest range. Variability in MMC concentration could cause inconsistency in glaucoma surgical results. However, the authors commented, the clinical relevance of such findings on glaucoma surgery outcomes remains unknown.
JAMA Ophthalmology summaries are based on authors’ abstracts, as edited by senior editor(s).
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