OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age >18 years, type 1 or 2 diabetes, central retinal thickness [CRT] ≥300 μm, and best corrected visual acuity [BCVA] of 73–39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n = 51 each) or sham (n = 49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n = 151, patients receiving ≥1 injection). RESULTS At month 12, mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham (P < 0.0001). Mean CRT reduction was 194.2 ± 135.1 μm with ranibizumab and 48.4 ± 153.4 μm with sham (P < 0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P < 0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab. CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.

Purpose. To investigate the association between subfoveal choroidal thickness and ocular axial length, refractive error, and blood pressure in healthy young women and men. Methods. Cross-sectional observational study of 93 eyes in 93 healthy Danish university students (mean age 24.9 ± 2.6 years). The submacular choroid was imaged using enhanced-depth imaging spectral domain optical coherence tomography. Subfoveal choroidal thickness was measured by visual inspection and manual fitting of the choroidal borderlines. Study parameters included history, best corrected visual acuity, objective refraction, interferometric ocular axial length, fundus photography, and blood pressure manometry. Results. The mean subfoveal choroidal thickness was 342 (±118) μm, the mean age was 24.9 (±2.6) years and the mean refractive error of participants was −1.43 (±2.9) diopters (D). In a multiple regression model, subfoveal choroidal thickness decreased by 58.2 μm (95% confidence interval [CI], 42.2–74.2 μm; P < 0.001) per mm increase in axial length adjusted for age and sex and subfoveal choroidal thickness was 62 μm (95% CI, 21–104 μm; P = 0.0039) thicker in men than in women, adjusted for age and axial length. Arterial blood pressure had no statistical effect on subfoveal choroidal thickness. Conclusions. In this study of healthy young participants choroidal thickness was 18% higher in men than in women when adjusting for age and axial length. This observation may help explain the effect of sex in conditions related to choroidal thickness such as myopia, central serous chorioretinopathy, and age-related macular degeneration.

To evaluate the efficacy and safety of ranibizumab 0.5 mg treat-and-extend (T&E) versus monthly regimens in patients with neovascular age-related macular degeneration (nAMD) from the TReat and extEND (TREND) study. A 12-month phase 3b visual acuity (VA) assessor-masked, multicenter, randomized, interventional study. Six hundred fifty patients. Treatment-naïve nAMD patients (age, ≥50 years) were randomized 1:1 to receive either a ranibizumab 0.5 mg T&E (n = 323) or monthly (n = 327) regimen. The primary objective was to show noninferiority of ranibizumab 0.5 mg T&E versus monthly regimen, as assessed by the change in best-corrected VA (BCVA) from baseline to the end of the study. Secondary objectives included change in retinal central subfield thickness (CSFT) from baseline to the end of study, treatment exposure, and safety. Overall, 89.8% (T&E) and 90.2% (monthly) of patients completed the study. Patient demographic and baseline characteristics were well balanced between the 2 treatment groups. The T&E regimen was noninferior (P < 0.001) to the monthly regimen, with a least squares mean BCVA change from baseline of 6.2 versus 8.1 letters to the end of study, respectively. In both treatment groups, most BCVA improvements occurred during the first 6 months and were maintained until the end of the study. The mean change in CSFT from baseline to the end of study was -169.2 μm and -173.3 μm in the T&E and monthly groups, respectively. Fewer injections were required in patients receiving the T&E (8.7) versus monthly (11.1) regimen, with mean number of postbaseline visits of 8.9 and 11.2, respectively. Types and rates of adverse events were comparable between the treatment groups. Ranibizumab 0.5 mg administered according to a T&E regimen was statistically noninferior and clinically comparable with a monthly regimen in improving VA from baseline to the end of study. No new safety signals for ranibizumab were identified.