This review describes a scheme for diagnosis of glaucoma in population based prevalence surveys. Cases are diagnosed on the grounds of both structural and functional evidence of glaucomatous optic neuropathy. The scheme also makes provision for diagnosing glaucoma in eyes with severe visual loss where formal field testing is impractical, and for blind eyes in which the optic disc cannot be seen because of media opacities.

https://bjo.bmj.com/content/bjophthalmol/86/2/238.full.pdf

The definition and classification of glaucoma in prevalence surveys

Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Background Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface. Methods We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surfa...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa040455

Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium.

An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration

https://oftalmologiarafaelcaiado.files.wordpress.com/2012/04/anchor-study.pdf

Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: Two-Year Results of the ANCHOR Study

Direct Cyclopexy for Traumatic Cyclodialysis with Persisting Hypotony: Report in 29 Consecutive Patients

PURPOSE. To identify and characterize genes differentially expressed in anterior segment tissues of eyes with pseudoexfoliation (PEX) syndrome and glaucoma. METHODS. Anterior segment tissues (iris, ciliary processes, lens epithelium) were obtained from eight surgically enucleated eyes with PEX-associated open-angle or closed-angle glaucomas and eight age-matched glaucomatous control eyes without PEX. cDNA libraries were generated from three PEX and three control specimens, and their gene expression patterns were compared by means of cDNA subtraction. Differentially expressed clones from the subtracted cDNA libraries were sequenced, and their differential expression was verified by means of RT-PCR, virtual Northern blot analysis, and in situ hybridization with specific RNA probes. RESULTS. Subtraction of cDNA libraries identified 27 candidate genes for differential expression in PEX tissues, of which 23 genes were confirmed by virtual Northern blot, RT-PCR, and in situ hybridization. One set of genes consistently upregulated in anterior segment tissues from different patients with PEX comprised latent transforming growth factor binding proteins (LTBP-1 and -2), which are structural components of elastic microfibrils, the cross-linking enzyme transglutaminase-2 (TGase-2), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), A-kinase anchor protein-2 (AKAP-2), apolipoprotein D, and the adenosine receptor-A3 (AdoR-A3). Genes reproducibly downregulated in PEX tissues included TIMP-1, clusterin, microsomal glutathione-S-transferase-1 (mGST-1), and serum amyloid A1. Further transcripts, such as elastase, GST-T1, integrin 4, and dehydrocholesterol reductase, did not show a consistent differential expression pattern in tissues obtained from different patients. Although fibrillin-1 was not isolated from subtracted cDNA libraries, upregulated expression of this elastic microfibrillar component was also demonstrated by RT-PCR and in situ hybridization. CONCLUSIONS. Differentially expressed genes with a high level of reproducibility in different tissues and different patients with PEX syndrome are mainly related to extracellular matrix metabolism and cellular stress. The underlying pathophysiology of PEX syndrome appears to be associated with an excessive production of elastic microfibril components, enzymatic crosslinking processes, a proteolytic imbalance between matrix metalloproteinases and their inhibitors, and increased cellular and oxidative stress supporting the notion of PEX syndrome as a stress-induced elastic microfibrillopathy. (Invest Ophthalmol Vis Sci. 2005;46:3742‐3752) DOI:10.1167/iovs.05-0249

Differential gene expression in pseudoexfoliation syndrome.

Pseudoexfoliation (PEX) syndrome is a generalized disease of the extracellular matrix and the most common identifiable cause of open-angle glaucoma. Two single nucleotide polymorphisms in the lysyl oxidase-like 1 (LOXL1) gene (rs1048661 and rs3825942) have been recently identified as strong genetic risk factors for both PEX syndrome and PEX glaucoma. Here we investigated the expression and localization of LOXL1, LOXL2, and lysyl oxidase (LOX) in tissues of PEX syndrome/glaucoma patients and controls in correlation with their individual single nucleotide polymorphism genotypes and stages of disease. LOXL1 ocular expression was reduced by approximately 20% per risk allele of rs1048661, whereas risk alleles of rs3825942, which were highly overrepresented in PEX cases, did not affect LOXL1 expression levels. Irrespective of the individual genotype, LOXL1 expression was significantly increased in early PEX stages but was decreased in advanced stages both with and without glaucoma compared with controls, whereas LOX and LOXL2 showed no differences between groups. LOXL1 was also found to be a major component of fibrillar PEX aggregates in both intra- and extraocular locations and to co-localize with various elastic fiber components. These findings provide evidence for LOXL1 involvement in the initial stages of abnormal fibrogenesis in PEX tissues. Alterations of LOXL1 activation, processing, and/or substrate specificity may contribute to the abnormal aggregation of elastic fiber components into characteristic PEX fibrils.

Genotype-Correlated Expression of Lysyl Oxidase-Like 1 in Ocular Tissues of Patients with Pseudoexfoliation Syndrome/Glaucoma and Normal Patients

Eyes with pseudoexfoliation syndrome (PEX) frequently show clinical signs of impairment of the blood-aqueous barrier. Herein we give an overview of recent studies that analyzed the blood-aqueous barri

Gottfried O. H. Naumann

Papers

Direct Cyclopexy for Traumatic Cyclodialysis with Persisting Hypotony: Report in 29 Consecutive Patients

Differential gene expression in pseudoexfoliation syndrome.

Genotype-Correlated Expression of Lysyl Oxidase-Like 1 in Ocular Tissues of Patients with Pseudoexfoliation Syndrome/Glaucoma and Normal Patients

The blood-aqueous barrier in eyes with pseudoexfoliation syndrome.

Anterior chamber depth and complications during cataract surgery in eyes with pseudoexfoliation syndrome.