However, several structural and functional differences support the fact that different mechanisms may have a stronger role in the pathogenesis of NTG versus high-pressure POAG. Also, a recent study reported genetic variants associated with different tendencies towards POAG with lower or higher IOP (6) . Furthermore, clinical impression and anecdotal evidence suggest that NTG with mean IOP in the high teens (>15 mmHg), in which circadian fluctuation and CCT could lead to a possible misdiagnosis of an IOP ≤21 mmHg, would differ from NTG with mean IOP in the low teens (≤15 mmHg), with different ABSTRACT Descritores: Glaucoma de ângulo aberto; Pressão in traocular; Doenças do nervo óptico; Anti-hipertensivos/uso terapêuticopathogenesis and progression patterns, harder to achieve target IOP, and higher incidence of disc hemorrhages. Nonetheless, a recent report does not support this assumption and underscores low-teens NTG as an important entity (7) . The proportion of NTG varies depending on different population studies. In Asian epidemiological protocols, NTG constituted the majority of open-angle glaucomas (52%-92%), depending on the country and study methodology (8) . Normal IOP was measured in 57.1% cases of POAG in a South African study (9) . In white populations, the proportion of NTG was lower than that observed in Asian and African populations. In studies conducted in the United States, Netherlands, and Italy, NTG presented proportions of 31. 7%, 38.9%, and 30%, respectively (10-12) . The etiology of NTG is most likely multifactorial and still not well defined. Moreover, several alternative treatments based on this different pathogenesis have been discussed. The objective of this study was to review the mechanisms involved in the onset and progression of NTG and the efficacy of established and alternative therapies for NTG treatment. PathogenesisThe pathogenesis of NTG is unclear, and perhaps the development of the disease is a consequence of a complex interaction of several systemic and ocular factors. Different studies have shown that the cardiovascular system and intracranial pressure may be involved in the main pathways of optic nerve damage. Nevertheless, the complex relationship between these mechanisms and glaucoma pro gression continues to be debated.

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Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice.

Our objective was to compare the diagnostic accuracies of and to determine the correlations between the disc damage likelihood scale (DDLS) and anatomical and functional tests used for glaucoma detection. A total of 54 healthy subjects (54 eyes) and 47 primary open-angle glaucoma patients (47 eyes) were included in this cross-sectional observational study. DDLS scores and cup-to-disc (C/D) ratios were evaluated. Subjects underwent standard automated perimetry (SAP), optic disc and retinal nerve fiber layer (RNFL) imaging with time and spectral-domain optical coherence tomography (TD and SD-OCT), Heidelberg Retina Tomograph (HRT II), and scanning laser polarimetry (GDx-VCC). Areas under the receiver operating characteristic curves (AROCs) for DDLS and diagnostic tests parameters were calculated. DDLS correlations (Spearman's rank) among these parameters were analyzed. Fifty-four eyes were healthy and 47 had glaucoma, including 16 preperimetric glaucoma. DDLS, vertical and horizontal C/D ratios had the largest AROCs (0.92, 0.94 and 0.91, respectively). DDLS diagnostic accuracy was better than the accuracies of HRT II parameters, TD and SD-OCT RNFL thicknesses, and SAP mean deviation (MD) index. There were no significant differences between the accuracies of the DDLS and the C/D ratios, TD-OCT vertical (0.89) and horizontal (0.86) C/D ratios, TD-OCT C/D area ratio (0.89), and GDx-VCC NFI (0.81). DDLS showed significant strong correlations with vertical (r = 0.79) and horizontal (0.74) C/D ratios, and with the parameters vertical C/D ratio and C/D area ratio from HRT II (both 0.77) and TD-OCT (0.75 and 0.72, respectively). DDLS had significant moderate correlations with most of the other structural measurements and SAP MD. The optic disc clinical evaluation with DDLS system and C/D ratio demonstrated excellent accuracy in distinguishing glaucomatous from healthy eyes. DDLS had moderate to strong correlations with most structural and functional parameters. These findings stress the importance of optic disc clinical examination to detect glaucoma in a clinical scenario.

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