Functions of individual matrix metalloproteinases (MMPs) differentially expressed by tumor cells and stromal cells, are finely regulated by their spatial as well as temporal interactions with distinct cellular and extracellular components of the tumor microenvironment and also distant pre-metastatic sites. Certain aspects of MMP involvement in tumor metastasis such as tumor-induced angiogenesis, tumor invasion, and establishment of metastatic foci at the secondary site, have received extensive attention that resulted in an overwhelming amount of experimental and observational data in favor of critical roles of MMPs in these processes. In particular, dependency of tumor angiogenesis on the activity of MMPs, especially that of MMP-9, renders this step possibly the most effective target of synthetic MMP inhibitors. MMP functioning in other stages of metastasis, including the escape of individual tumor cells from the primary tumor, their intravasation, survival in circulation, and extravasation at the secondary site, have not yet received enough consideration, resulting in insufficient or controversial data. The major pieces of evidence that are most compelling and clearly determine the role and involvement of MMPs in the metastatic cascade are provided by molecular genetic studies employing knock-out or transgenic animals and tumor cell lines, modified to overexpress or downregulate a specific MMP. Findings from all of these studies implicate different functional mechanisms for both tumor and stromal MMPs during distinct steps of the metastatic cascade and indicate that MMPs can exhibit pro-metastatic as well as anti-metastatic roles depending on their nature and the experimental setting. This dual function of individual MMPs in metastasis has become a major focus of this review.

Matrix metalloproteinases and tumor metastasis

As their name implies, matrix metalloproteinases are thought to be responsible for the turnover and degradation of the extracellular matrix. However, matrix degradation is neither the sole nor the main function of these proteinases. Indeed, as we discuss here, recent findings indicate that matrix metalloproteinases act on pro-inflammatory cytokines, chemokines and other proteins to regulate varied aspects of inflammation and immunity.

Matrix metalloproteinases as modulators of inflammation and innate immunity

Descemet's stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.

Matrix metalloproteinases (MMPs) have outgrown the field of extracellular-matrix biology and have progressed towards being important regulatory molecules in cancer and inflammation. This rise in status was accompanied by the development of various classes of inhibitors. Although clinical trials with synthetic inhibitors for the treatment of cancer were disappointing, recent data indicate that the use of selective inhibitors might lead to new therapies for acute and chronic inflammatory and vascular diseases. In this Review, we compare the major classes of MMP inhibitors and advocate that future drug discovery should be based on crucial insights into the differential roles of specific MMPs in pathophysiology obtained with animal models, including knockout studies.

Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases

In response to a perceived need in the vision community, an OSA taskforce was formed at the 1999 topical meeting on vision science and its applications (VSIA-99) and charged with developing consensus recommendations on definitions, conventions, and standards for reporting of optical aberrations of human eyes. Progress reports were presented at the 1999 OSA annual meeting and at VSIA-2000 by the chairs of three taskforce subcommittees on (1) reference axes, (2) describing functions, and (3) model eyes.

Standards for reporting the optical aberrations of eyes

PURPOSE. To investigate the efficacy of topography and tomography indices combined in discriminant functions to detect mild ectatic corneas. METHODS. The authors retrospectively reviewed the data of 143 eyes separated into three groups by the Corneal Navigator OPD scanning system (Nidek, Gamagori, Japan): normal (N; LASIK surgery with a 2-year follow-up; n 72), forme fruste keratoconus (N topography with contralateral KC; FFKC; n 40), and KC (n 31). Topography and tomography indices, corneal thickness spatial profile (CTSP), and anterior and posterior curvature spatial profiles were obtained with the Orbscan IIz (Bausch & Lomb Surgical, Rochester, NY). The percentage of thickness increase (PTI) from the thinnest point to the periphery, the percentage of variation of anterior (PVAK), and posterior curvature were calculated and compared by Kruskal-Wallis test. The usefulness of these data to discriminate among the three groups was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS. Posterior elevation of the thinnest point (TP), all positions of CTSP, PTI for all distances from the TP, and PVAK from a 5- to 7-mm distance from the TP were significantly different in the FFKC compared with the N group. The discriminant functions between the FFKC and the N groups and between the KC and the N groups reached an area under the ROC curve of 0.98 and 0.99, respectively. PTI indices and maximum posterior central elevation were the most important contributors to the discriminant function. CONCLUSIONS. Indices generated from corneal thickness and curvature measurements over the entire cornea centered on the TP can identify very mild forms of ectasia undetected by a Placido-based neural network program. (Invest Ophthalmol Vis Sci. 2010;51:5546‐5555) DOI:10.1167/iovs.10-5369

/pdf/topographic-and-tomographic-properties-of-forme-fruste-i9xsqcnniu.pdf

Topographic and tomographic properties of forme fruste keratoconus corneas.

Multifocal and Extended Depth-of-Focus Intraocular Lenses in 2020.

Purpose To assess the differences in optical performance of 9 multifocal IOLs using the same optical bench and to propose a possible comparison for surgeons. Setting Rothschild Foundation, Paris, France. Design Experimental study. Methods Nine IOLs (Acrysof Restor +3.0 diopter [D] SN6AD1, Acrysof Restor +4.0 D SN60D3, Acrysof aspheric monofocal SN60WF, Acri.Lisa 366D, Finevision Micro F, Tecnis ZM900, and Rezoom, Diffractiva Diff-s, and Lentis Mplus +3.0 D) were tested using the same optical bench that complies with International Organization for Standardization standard 11979 requirements. The through-focus modulation transfer functions (MTFs) were compared, and the image of the United States Air Force (USAF) target was taken while each IOL was at far, intermediate, and near focal points. Results The through-focus MTF of the trifocal IOL showed a peak in the intermediate range that was not present with monofocal and bifocal IOLs. The USAF target images showed similar resolution with all IOLs for far focal points. Diffractive IOLs showed better resolution for near focal points, and the only sharp image in the intermediate range was obtained using the trifocal IOL. Conclusion There was a significant difference in the degree of near, intermediate, and distance quality of the image with the various types of multifocal IOLs in vitro. Intermediate vision was more prominent with the trifocal IOL. Financial Disclosure Dr. Gatinel has a proprietary interest in the optical frame used (Patent WO2011092169 [A1] 2011-08-04). Dr. Houbrechts has no financial or proprietary interest in any material or method mentioned.

/pdf/comparison-of-bifocal-and-trifocal-diffractive-and-38j7kuu6ff.pdf

Comparison of bifocal and trifocal diffractive and refractive intraocular lenses using an optical bench.

Purpose To compare the anterior and posterior corneal elevation maps between keratoconus-suspect eyes and normal eyes. Setting Rothschild Foundation, AP-HP, University Paris VII, Hopital Bichat Claude Bernard, Paris, France. Methods The anterior and posterior corneal surface elevations were analyzed and compared in 60 normal myopic patients and 48 keratoconus-suspect patients. The anterior and posterior best-fit sphere radii, central and thinnest corneal pachymetries, anterior and posterior aconic shape parameters (aconic radius, aconic asphericity, aconic toricity), and anterior and posterior elevation in the 1.0 mm radius zone were analyzed. The correlations between elevation and aconic shape parameters between the anterior and posterior surfaces were compared. Results The mean central and thinnest pachymetry values were significantly lower in keratoconus-suspect eyes ( P P = .0002) and posterior toricity ( P P = .042), and higher posterior elevation ( P Conclusions The posterior corneal elevation and the corneal thickness values were different in keratoconus-suspect eyes. The correlation between the anterior and posterior corneal aconic shapes was between keratoconus-suspect eyes and normal eyes.

https://www.gatinel.com/wp-content/uploads/2010/01/JCRS-MAY-2008.pdf

Comparison of and correlation between anterior and posterior corneal elevation maps in normal eyes and keratoconus-suspect eyes.

Purpose To evaluate the repeatability of measurements with a double-pass system. Setting Rothschild Foundation, Paris, France. Methods Eyes were separated into 2 control groups ( 40 years), a post-refractive surgery group, and a cataract group. Measurements were performed using the Optical Quality Analysis System. The main outcome measures were the objective scattering index (OSI), the cutoff frequency of the modulation transfer function (MTF), and the Strehl ratio. The repeatability limit was obtained from the individual standard deviations. Results Forty-two eyes were evaluated. The mean OSI value was 0.47 ± 0.11 (SD) in the younger control group, 1.73 ± 0.26 in the older control group, 1.34 ± 0.16 in the post-refractive surgery group, and 6.15 ± 0.50 in the cataract group. The mean cutoff MTF value was 39.44 ± 3.93 cycles per degree (cpd), 26.07 ± 3.89 cpd, 28.34 ± 2.84 cpd, and 13.3 ± 1.69 cpd, respectively, and the mean Strehl ratio, 0.234 ± 0.023, 0.146 ± 0.021, 0.169 ± 0.023, and 0.098 ± 0.010, respectively. The repeatability limit for the whole population was 0.841 (33.5%) for the OSI, 8.499 (31.1%) for the cutoff MTF, and 0.051 (31%) for the Strehl ratio. Conclusions The repeatability limit was good and equivalent for the OSI, the MTF, and the Strehl ratio values. There was a wide interval between the normal and pathologic threshold for OSI measurements, indicating that the reliability of the double-pass device complies with the requirements for quantitative assessment of scattering. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

/pdf/repeatability-of-measurements-with-a-double-pass-system-4e18rbdu6z.pdf

Repeatability of measurements with a double-pass system

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