. Purpose:  To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age‐related macular degeneration (AMD). Methods:  Forty‐three patients with exudative AMD and 19 age‐ and sex‐matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4‐weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. Results:  At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty‐eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab‐treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab‐treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. Conclusions:  Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time‐point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.

BackgroundThe aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid.MethodsIn 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated.ResultsThere was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 μm (P<0.001), and in vertical scans, the mean increase was +8.80±7.07 μm (P=0.001). However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 μm; P=0.47) whilst in horizontal scans a nonsignificant decrease was recorded (−9.11±39.59 μm; P=0.41). In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 μm; P=0.36).ConclusionUncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of phacoemulsification is mainly observed at the retinal level, and seems to be independent of choroidal thickness changes.

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Purpose: To report the clinical outcomes of intravitreal aflibercept therapy in eyes with refractory and recurrent neovascular age-related macular degeneration (AMD) switched from intravitreal bevacizumab or ranibizumab. Methods: This is a retrospective review of eyes with neovascular AMD switched to intravitreal aflibercept with at least 1 year of follow-up after the switch. All patients had had a minimum of 3 injections of bevacizumab or ranibizumab before the switch. Aflibercept was used in patients considered refractory to bevacizumab (group 1) and in recurrent patients on therapy with ranibizumab due to an institutional policy decision (group 2). Changes in best-corrected visual acuity, fluid on optical coherence tomography (OCT), central retinal thickness (CRT) and the frequency of injections were compared. Results: Eighty-five eyes of 69 patients were analyzed, 39 eyes in group 1 and 46 in group 2. The mean follow-up time was 31.6 months prior to the switch and 14.7 months on treatment with aflibercept. One year after the switch, there was a nonsignificant mean decrease of 2 letters in visual acuity in both groups (group 1: from 58.2 to 55.8 letters, p = 0.086; group 2: from 56.4 to 54.5 letters, p = 0.168), but the mean number of injections per month was significantly lower (from 0.76 to 0.57, p < 0.001). With the switch, 90.6% of the patients showed anatomic improvement with a reduction of fluid on OCT, and both groups presented significant improvement in CRT (group 1: 65.3 µm, p = 0.051; group 2: 91.0 µm, p < 0.001). Conclusion: Aflibercept appears to be a valuable tool for the management of patients with poor responses to other anti-vascular endothelial growth factor drugs. These patients could have anatomic improvement, and the injection intervals could be extended.

Background/Aims: To compare retrospectively the incidence of arterial thromboembolic events (ATEs) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration. Methods: Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were reviewed to calculate the incidence of ATEs. Only patients under monotherapy were analyzed. Results: ATEs occurred in 15 patients: 12 (12/97) with bevacizumab (12.4%) and 3 (3/219) with ranibizumab (1.4%) – odds ratio 10.16; 95% confidence interval 2.80–36.93; p < 0.0001. ATEs in the bevacizumab and ranibizumab cohorts included stroke, myocardial infarction, angina pectoris, peripheral thromboembolic disease, transient ischemic attack, sudden death and lethal stroke. Conclusion: In this series, bevacizumab raised the risk of ATEs when compared to ranibizumab. In an elderly population with multiple cardiovascular risk factors, the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration. These findings raise an issue that must be confirmed in randomized clinical trials.

Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1e5 human ghrelin (frGhr, 10 À9 À6 Â 10 À5 M) and 1e5 human des-octanoyl-ghrelin (d-frGhr; 10 À9 À6 Â 10 À5 M) were tested on iris rabbit sphincter (n ¼ 11 frGhr; n ¼ 7 d-frGhr), dilator (n ¼ 6 frGhr; n ¼ 6 d-frGhr) and rat sphincter (n ¼ 6 frGhr; n ¼ 8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10GHRP6 (10 À4 M; n ¼ 6); and iv) apamin þ carybdotoxin (10 À6 M; n ¼ 6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys 3 GHRP6 (10 À4 M; n ¼ 7). Finally, ghrelin mRNA production was assessed by ''in situ'' hybridization in Wistar rat eyes (n ¼ 8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 Â 10 À5 M, 1.5e3 min after its addition, decreasing tension by 34.1 AE 12.1%, 25.8 AE 4.8% and 52.1 AE 10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys 3 GHRP6 (118.1 AE 21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin þ carybdotoxin (36.4 AE 14.4%) or L-NA (52.4 AE 11.4%). Relaxing effects of d-frGhr in rabbit (43.3 AE 5.2%) and rat (77.1 AE 15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K Ca channels.

Aim: Evaluation of safety and efficacy of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) secondary to causes other than age-related macular degeneration (AMD) or pathological myopia (PM). Methods: Retrospective and multicentric analysis of 21 eyes with CNV. Nine eyes had angioid streaks, 5 inflammatory chorioretinal diseases, 3 central serous chorioretinopathy and 4 idiopathic CNV. Follow-ups lasted ≧3 months. Best-corrected visual acuity (BCVA), ocular coherence tomography (OCT) and fundus examination were assessed monthly. Results: Sixteen eyes (76%) completed 180 days of follow-up. Overall BCVA increased by +9.8 letters with treatment (p = 0.015). Visual acuity improvements ≧15 letters occurred in 43%. A significant reduction in OCT central thickness was observed. No cases of severe visual acuity loss, systemic or ocular side effects were registered. Conclusion: Short-term results of intravitreal ranibizumab for CNV unrelated to AMD or PM are encouraging. This treatment may constitute the only option for some of these patients.

The choroid may be subclinically involved in autoimmune diseases. However, the choroidal response seems to differ depending on the autoimmune disease. Infiltrative mechanisms specific for lupus may justify the thickened choroid found in these patients.