Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-β superfamily (TGF-β1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40942-017-0084-9) contains supplementary material, which is available to authorized users.

Purpose To evaluate the expression of 19 angiogenic biomarkers in the aqueous humor before and after intravitreal bevacizumab injection (IVB) in eyes with neovascular age-related macular degeneration (AMD). Design Prospective, noncomparative, interventional case series. Participants Twenty-three eyes of 23 treatment-naïve patients with choroidal neovascularization (CNV) secondary to neovascular AMD. Methods Eyes were diagnosed with CNV secondary to neovascular AMD and were treated with 3 monthly IVBs. Aqueous humor samples were obtained by anterior chamber paracentesis at baseline and immediately before each intravitreal bevacizumab injection. Main Outcome Measures Aqueous humor levels of 19 angiogenic biomarkers (angiopoietin 2, bone morphogenetic protein 9 [BMP-9], epidermal growth factor [EGF], endoglin, endothelin 1, fibroblast growth factor [FGF]-1 and FGF-2, follistatin, granulocyte colony-stimulating factor [GCSF], heparin-binding EGF-like growth factor [HB-EGF], hepatocyte growth factor [HGF], interleukin 8, leptin, placental growth factor [PLGF], vascular endothelial growth factor [VEGF]-A, VEGF-C, VEGF-D, and tissue inhibitor of metalloproteinases [TIMP]-1 and TIMP-2) were measured. Best-corrected visual acuity (BCVA), spectral-domain OCT parameters, and intraocular pressure also were evaluated. Results Baseline aqueous VEGF-A expression was elevated in all study eyes before treatment initiation. A statistically significant decrease of VEGF-A was observed at the 1- and 2-month follow-ups. A statistically significant increased concentration was observed in 7 biomarkers: VEGF-C, angiopoietin 2, endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8. The other 11 study biomarker levels (VEGF-D, BMP-9, EGF, endoglin, FGF-1, FGF-2, GCSF, leptin, PLGF, TIMP-1, and TIMP-2) did not show any significant difference during follow-up. The BCVA statistically improved significantly at 2 months. Spectral-domain OCT parameters improved significantly at all follow-ups. Mean intraocular pressure values were not statistically different during the study period. Conclusions Despite a decrease in VEGF-A, the aqueous levels of VEGF-C, angiopoietin 2, endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8 increased significantly after intravitreal injection of bevacizumab. These upregulated angiogenic biomarkers may represent new therapeutic targets in exudative AMD.

Purpose: To evaluate the concentration of vascular endothelial growth factor (VEGF) in aqueous humor after a single intravitreal injection of bevacizumab (IVB) in eyes with neovascular age-related macular degeneration (AMD). Methods:In this prospective interventional case series study, 24 eyes of 24 patients with types 1 and 2 choroidal neovascularization secondary to neovascular AMD were treated with a single intravitreal injection of bevacizumab. Aqueous humor samples were obtained before the intravitreal injection and at one week, one month, and three months follow-up periods. Best-corrected visual acuity (BCVA) and three spectral-domain optical coherence tomography parameters (central retinal thickness, macular volume and macular area) were also analyzed and correlated with VEGF expression at the baseline and each follow-up period.Results: All of the ninety-six aqueous humor study taps were well tolerated by the study patients without adverse events. Increased VEGF levels (mean ± SD = 179.7 ± 88.3 pg/mL) were observed in the aqueous humor of all study patients before the intravitreal injection of bevacizumab. At all follow-up periods, compared to baseline, levels of VEGF significantly reduced (P < 0.0001), and BCVA significantly improved (P < 0.005). The lowest VEGF expression was observed at 1 week, and the greatest BCVA improvement occurred 1 month after treatment. At 1 month, central retinal thickness (CRT), macular volume (MV), and macular area (MA) significantly reduced compared to baseline (P < 0.0001, P = 0.0005, P = 0.007, P = 0.009, respectively). At 1 week and 3 months, although without statistical significance (P > 0.005), CRT, MV and MA also reduced in comparison to baseline. Conclusions: Single intravitreal bevacizumab injection in eyes with neovascular AMD resulted in a substantial decrease of aqueous VEGF levels 1 week after treatment with the greatest improvement of clinical outcomes occurring at 1 month follow-up.

Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.

RESUMOObjetivo: Comparar a pressão intraocular (PIO) pré e pós-LASIK, correlacionando-as com as mudanças da espessura corneana central (ECC) e ceratometria simulada média (K), assim como verificar o resultado de fórmula corretiva proposta anteriormente. Métodos: Estudo longitudinal, prospectivo, realizado em pacientes submetidos a LASIK. Os pacientes foram submetidos ao exame oftalmológico completo, no pré-operatório e após 2 meses da cirurgia. A pressão intraocular foi avaliada com tonô-metro de aplanação de Goldmann entre 9 h e 11 h da manhã, a ceratometria simulada média foi avaliada por meio de topografia corneana e a espessura corneana central foi aferida por paquímetro ultrassônico, sendo considerada a média de três aferições. Foram excluídos dois pacientes com cirurgias ou doenças oculares prévias, e uso prévio de corticosteróide tópico nos últimos três meses. As cirurgias foram realizadas de acordo com os procedimentos-padrão. Foi utilizada a fórmula [PIO real = PIO aferida + (540 -ECC)/71 + (43 -K)/2,7 + 0,75 mmHg] proposta para correção da pressão intraocular pós-operatória. Resultados: Quinze olhos de oito pacientes foram avaliados, a idade variou de 24 a 46 anos (média: 31,37 ± 7,27). Foi observada diferença estatisticamente significante entre as medidas da pressão intraocular, de ceratometria simulada média e da espessura corneana central pré e pós-LASIK. (p=0,0001). Foi observado que para cada 1D corrigida, há uma subestimação, em média, de 1,06 ± 0,59 mmHg (0,11 a 1,89 mmHg). A aplicação da fórmula corretiva levou a 80% dos olhos com a tonometria estimada entre ± 2,50 mmHg da pré-operatória, no entanto, quando comparada com a tonometria pré-operatória, estas são estatisticamente diferentes (p=0,0266). Conclusões: Os olhos submetidos a LASIK apresentaram PIO pós-operatória menor do que a pré-operatória. A pressão intraocular pôde ser moderadamente correlacionada com a espessura corneana central e fracamente com a ceratometria simulada média. Não houve correlação entre a profundidade de ablação e a variação da pressão intraocular, no pós-operatório. Usando a fórmula proposta, pudemos averiguar que 80% dos pacientes apresentaram pressão intraocular entre ± 2,50 mmHg da pré-operatória. Descritores INTRODUÇÃODesde 1993, LASIK (laser in situ keratomileusis) é a técnica cirúrgica mais executada pelos cirurgiões refrativos (1) , não só pela rápida recuperação visual, como também pela possibilidade de correção das ametropias mais altas (2) . A correção é obtida pela Correspondence address: Thiago George Cabral Silva. Departamento de Oftalmologia HSPE/SPAv. Ibirapuera, 981 -São Paulo -SP -04029-000 -Brazil E-mail: thiagogeorge@hotmail.com alteração da curvatura anterior da córnea, havendo diminuição da sua espessura secundária à ação do laser. Entretanto, essas mudanças estruturais estão correlacionadas com leituras subestimadas da pressão intraocular (PIO) no pós-operatório pelo tonômetro de aplanação de Goldmann (TAG) (3) .

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Keratoconus (KC) is likely to be more aggressive in the pediatric population, with a higher risk of progression and visual loss. Several techniques have been proposed for corneal crosslinking (CXL) so far. The standard CXL (SCXL) technique, or the Dresden Protocol, originally developed by Wollensak et al., has been shown to be safe and effective in the pediatric KC group. With similar efficacy to the conventional method, the accelerated CXL (ACXL) protocols proposed a reduced UVA exposure time by increasing the intensity of UVA irradiation. Transepithelial CXL (TCXL), considered an “epithelium-on” method, emerged as a strategy to improve safety and reduce postoperative complications and discomfort. For thinner corneas, we can highlight the use of hypoosmolar riboflavin and new studies, such as contact lens-assisted CXL (CACXL), the epithelial-island CXL (EI-CXL), and the Sub400 protocol. In addition to the different protocols used, another factor that changes CXL results is the type of carrier used: dextran-based or hydroxypropyl methylcellulose-based (HPMC) riboflavin solutions. There are several ways to perform a CXL surgery, and it is still unclear which method is the safest and most effective in the pediatric group. This review of the literature in English, available in PubMed, provides an update on corneal CXL in the pediatric KC group, exploring the data on the techniques currently used and under investigation, including their advantages, efficacy, safety profiles, risks, and cost analyses.

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