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Introduction Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting. Methods This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at Month 6. Secondary endpoints were mean changes from baseline in BCVA at Month 24 and central retinal thickness (CRT) at Months 6 and 24, and treatment use in real-world setting. Results 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5) and 11.4 (20.1) letters at Months 3, 6, 12 and 24. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7) and 8.3 (23.8) letters at Months 3, 6, 12 and 24. At Month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 550 (175), 315 (104), 343 (122), 335 (137) and 340 (105) μm. In CRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 643 (217), 327 (152), 400 (203), 379 (175) and 348 (161) μm. On average, BRVO patients had 3.8 injections for 6.9 visits by Month 6, and 7.2 injections for 19.7 visits by Month 24. CRVO patients had 2.7 injections for 4.2 visits by Month 6, and 7.1 injections for 21.1 visits by Month 24. Factors predictive of better BCVA gain at Month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at Month 3. There were no new safety findings. Conclusion Major improvements in BCVA and CRT were observed at Month 3 after the induction phase, and then was sustained up to Month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or pro-active treatment could further improve outcomes.

Purpose: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME). Methods: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, precision = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events. Results: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 μm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA >70 letters versus 13.2% at baseline. Mean change in CSFT was −125 μm (95% CI: −146, −103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified. Conclusions: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials.

Retinal vein occlusions (RVOs) have been defined as retinal vascular disorders characterized by dilatation of the retinal veins with retinal and subretinal hemorrhages and macular edema, and/or retinal ischemia. Fluorescein angiography (FA) remains essential for the diagnosis and prognosis of RVO, allowing recognition of the diverse types of RVO, such as perfused or nonperfused, as well as detection of the different modalities in natural history. F A is the most effective method to determine the presence (or absence) of macular cystoid edema, its extension, persistence, regression, or the degree of ischemia. Spectral domain optical coherence tomography (SD-OCT) helps to quantify the changes in retinal thickness, the amount of cystoid macular edema, and supplies additional information, such as whether the accumulated fluid is located mostly within the retinal layers or additionally in the sub retinal space. SD-OCT can display the presence and integrity of the outer limiting membrane and of the inner and outer segments of the photoreceptors, useful information for prognosis and a guide for treatment in the management of RVO. Laser photocoagulation in a 'grid' pattern over the area, demonstrated as leaking by FA, remains the 'reference treatment for macular edema due to branch retinal vein occlusion', according to the recent results of the SCORE Trial. Recent case series studies and prospective randomized trials strongly suggest an antiedematous effect of intravitreal steroids and an associated improvement in vision. These studies have suggested that intravitreal steroids (triamcinolone, fluocinolone, dexamethasone in a slow-release device) and intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, pegabtanib) may at least temporarily reduce foveal edema and correspondingly improve visual function. Surgical treatment modalities have been reported for RVOs. The positive action of vitrectomy seems durable; the combination of surgery and intravitreal injection of steroids and/or an injection of tissue plasminogen activator could permit a more rapid and lasting action. However, strong data from randomized trials are warranted.

The rabbit corneal angiogenesis assay was modified to allow quantification of the neovascular response induced by growth factors. Basic Fibroblast Growth Factor (bFGF) was used for this experiment. bFGF was diluted in phosphate buffer solution (PBS) in such a way that 2 microliter of solution contained concentrations ranging from 17 to 1,200 ng. Each drop was absorbed by a 1 x 2 mm particle of a dried 70% hydratable hydrogel and implanted into a mid-stroma corneal pocket, 2 mm from the limbus. Iodinated bFGF was used to measure growth factor diffusion in the cornea, which was found to be isotropic. Autoradiography showed that bFGF was stored in the cornea at both epithelial and endothelial level. Corneal neovascularization occurred on the second day after implantation and was maximal on the 7th day. At this time the neovascular surface was measured by planimetry on corneal photographs and compared with controls. This method allows precise definition of the dose of any substance to be implanted into the cornea and induces a rapid neovascular response, thus allowing quantitative evaluation of neovascularization within one week. A neovascular response was detectable for doses as low as 35 ng of bFGF and increased proportionally to the dose of bFGF implanted.