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

Four hundred and fifty-seven unselected normal human optic nerve heads of 319 subjects (163 men, 156 women, mean age 42.7 +/- 19.6 years) were evaluated by magnification-corrected morphometry of optic disc photographs. Mean optic disc surface measured 2.69 +/- 0.70 mm2 (0.80-5.54 mm2), mean diameter horizontally 1.76 +/- 0.31 mm (0.91-2.61 mm), and vertically 1.92 +/- 0.29 mm (0.96-2.91 mm). The form was slightly vertically oval. Optic cup area averaged 0.72 +/- 0.70 (0.00-3.41 mm2), mean horizontal cup diameter 0.83 +/- 0.58 mm (0.00-2.08 mm) and mean vertical diameter 0.77 +/- 0.55 mm (0.00-2.13 mm). The cup was significantly (P less than 0.0001) larger in discs with steep "punched-out" cups (1.37 +/- 0.62 mm2) compared to discs having cups with temporal flat slopes (0.59 +/- 0.39 mm2). Neuroretinal rim area ranged from 0.80 to 4.66 mm2 (mean 1.97 +/- 0.50 mm2), and was significantly correlated (P less than 0.00001) to the optic disc area. It was broadest in the inferior optic disc region (P less than 0.001), followed by the superior, nasal and temporal (P less than 0.001) regions. Horizontal cup/disc ratio (mean 0.39 +/- 0.28, minimum 0.00, maximum 0.87) was larger in 426 (93.2%) optic discs than the vertical one (mean 0.34 +/- 0.25, minimum 0.00, maximum 0.85). Concerning optic disc area, side differences of 0.10 mm2 or less were detected in 28%, of 0.2 mm2 or less in 46% and of 0.50 mm2 or less in 80% (cumulative frequencies). Concerning neuroretinal rim area, side differences of 0.10 mm2 or less were found in 31%, of 0.20 mm2 or less in 52% and of 0.50 mm2 or less in 84%.(ABSTRACT TRUNCATED AT 250 WORDS)

Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes.

Ocular and Systemic Pseudoexfoliation Syndrome

The pseudoexfoliation syndrome has recently been suggested to represent the local manifestation of a more widespread disorder. In this study, a case of classic bilateral pseudoexfoliation syndrome with systemic distribution of pseudoexfoliation material involving a variety of organ systems is described. Using transmission electron microscopy, typical pseudoexfoliation fibers were identified in autopsy tissue specimens of skin, heart, lungs, liver, kidney, and cerebral meninges in addition to the classic intraocular locations. The pseudoexfoliation material was mainly localized to connective-tissue portions or septa traversing the various organs. The pseudoexfoliation fibers were consistently associated with connective-tissue components, particularly fibroblasts and collagen and elastic fibers; myocardial tissue specimens; and heart-muscle cells. These findings provide evidence for the systemic nature of the pseudoexfoliation syndrome, which apparently involves an aberrant connective-tissue metabolism throughout the body.

Pseudoexfoliation syndrome, ocular manifestation of a systemic disorder?

Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations.

Purpose To evaluate the impact of photodynamic therapy (PDT) on expression and distribution of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-3, and pigment epithelium-derived factor (PEDF). Methods Eyes of patients scheduled for enucleation due to untreatable malignancy served as study eyes (n = 4), age-matched donor eyes were used as the control (n = 4). PDT using verteporfin with the recommended standard parameters was applied to intact areas of the perimacular region. Lesions were classified by ophthalmoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), as well as light and electron microscopic (LM/EM) histology. Immunolabeling using specific antibodies against VEGF, VEGFR-3, and PEDF was performed in PDT-treated areas, untreated collateral areas in study eyes, and untreated areas of control eyes. Specimens were fixed in 4% paraformaldehyde and 1% glutaraldehyde and embedded in paraffin. Four-micrometer-thick sections were stained using the peroxidase-labeled streptavidin-biotin method. Results All PDT-treated areas demonstrated characteristic choroidal hypofluorescence by FA and ICGA. LM/EM histology revealed selective damage of choriocapillary endothelial cells. VEGF was expressed in the endothelial layer of choriocapillaries and focally within larger choroidal vessels in treated areas, but not in untreated areas. Sites with positive VEGF labeling also demonstrated upregulation of VEGFR-3. PEDF expression was localized to retinas in all eyes; however, PEDF staining of choroidal endothelial cells was specific for treated areas of study eyes. Conclusions PDT using verteporfin induces a reproducible angiogenic response in elderly human eyes. VEGF, VEGFR-3, and PEDF expression is enhanced after PDT. Choroidal endothelial cells appear to be the primary site of angiogenic stimulation.

Gottfried O. H. Naumann

Papers

Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes.

Ocular and Systemic Pseudoexfoliation Syndrome

Pseudoexfoliation syndrome, ocular manifestation of a systemic disorder?

Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations.

Influence of Photodynamic Therapy on Expression of Vascular Endothelial Growth Factor (VEGF), VEGF Receptor 3, and Pigment Epithelium–Derived Factor