OLIMPIC : a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV). Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab. Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22\u201385 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03\u2013124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55\u2013513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39\u2013222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1\u20139. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively. Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings. Trial registration: www.ClinicalTrials.Gov (NCT No: NCT02034006)

New Brilliant Blue G Derivative as Pharmacological Tool in Retinal Surgery.

Our study was aimed at assessing the retinal binding of a new synthetic Brilliant Blue G (BBG) derivative (pure benzyl-Brilliant Blue G; PBB) ophthalmic formulation, to improve vitreoretinal surgery procedure. Protein affinity of the new molecule was evaluated in vitro (cell-free assay) and in silico. Furthermore, an ex vivo model of vitreoretinal surgery was developed by using porcine eyes to assess the pharmacological profile of PBB, compared to commercial formulations based on BBG and methyl-BBG (Me-BBG). PBB showed a higher affinity for proteins (p < 0.05), compared to BBG and Me-BBG. In vitro and in silico studies demonstrated that the high selectivity of PBB could be related to high lipophilicity and binding affinity to fibronectin, the main component of the retinal internal limiting membrane (ILM). The PBB staining capabilities were evaluated in porcine eyes in comparison with BBG and Me-BBG. Forty microliters of each formulation were slowly placed over the retinal surface and removed after 30 s. After that, ILM peeling was carried out, and the retina collected. BBG, Me-BBG, and PBB quantification in ILM and retina tissues was carried out by HPLC analysis. PBB levels in the ILM were significantly (p < 0.05) higher compared to BBG and Me-BBG formulations. On the contrary, PBB showed a much lower (p < 0.05) distribution in retina (52 ng/mg tissue) compared to BBG and Me-BBG, in particular PBB levels were significantly (p < 0.05) lower. Therefore, the new synthetic Brilliant Blue derivative (PBB) showed a great ILM selectivity in comparison to underneath retinal layers. In conclusion, these findings had high translational impact with a tangible improving in ex vivo model of retinal surgery, suggesting a future use during surgical practice

Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p < 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p < 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p < 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p < 0.05) after retinal I/R insult and increased significantly (p < 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury