Predictive factors of the optic nerve head for development or progression of glaucomatous visual field loss

PURPOSE: To evaluate which morphologic features of the optic disc are predictive factors for the development or progression of visual field loss in chronic open-angle glaucoma. METHODS: The prospective observational clinical study included 763 eyes of 416 white subjects with ocular hypertension and chronic open-angle glaucoma. During the follow-up time (mean, 67.4 months; median, 65.1; range, 6.2-104.5), all patients underwent repeated qualitative and morphometric evaluation of color stereo optic disc photographs and white-on-white visual field examination. Progression of glaucomatous visual field damage was defined by point-wise regression analysis for each of the 59 locations in the visual field. Outcome measures were qualitative and quantitative morphologic optic nerve head parameters. RESULTS: Development or progression of glaucomatous visual field defects was detected in 106 (13.9%) eyes. At baseline of the study, neuroretinal rim area was significantly (P < 0.002) smaller, the beta zone of parapapillary atrophy (P < 0.003, nasal sector) was significantly larger, and age was significantly higher (P < 0.003) in the progressive study group than in the nonprogressive study group. Both study groups did not vary significantly in size of the optic disc and the alpha zone of parapapillary atrophy. Cox proportional hazard regression analysis revealed that the progression of glaucomatous visual field loss depended significantly on the area of the neuroretinal rim (P < 0.001) and age (P < 0.001), but was independent of diameter of the retinal arterioles and veins. CONCLUSIONS: Morphologic predictive factors for development or progression of glaucomatous visual field defects in whites are small neuroretinal rim area and large beta zone of parapapillary atrophy. Age is an additional nonmorphologic parameter. Progression of glaucomatous optic nerve head changes is independent of the size of the optic disc and alpha-zone of parapapillary atrophy and retinal vessel diameter.     

Inhibition of tumor-induced angiogenesis and matrix-metalloproteinase expression in confrontation cultures of embryoid bodies and tumor spheroids by plant ingredients used in traditional chinese medicine

Tumor-induced angiogenesis is a prerequisite for excessive tumor growth. Blood vessels invade the tumor tissue after degradation of the extracellular matrix scaffold by matrix metalloproteinases (MMPs). Inhibition of MMPs has been therefore suggested to be a useful tool to abolish neoangiogenesis of solid tumors. In the present study, antioxidative plant ingredients used in traditional Chinese medicine were investigated for their capacity to down-regulate MMP expression and to inhibit angiogenesis in embryonic stem cell-derived embryoid bodies and tumor-induced angiogenesis in confrontation cultures consisting of embryoid bodies and multicellular DU-145 prostate tumor spheroids. Embryoid bodies transiently expressed MMP-1, MMP-2, and MMP-9 during the time of differentiation of capillary-like structures. In confrontation cultures, MMP expression was increased compared with control tumor spheroids and embryoid bodies cultivated separately. The increased expression of MMPs in confrontation cultures was a result of elevated levels of reactive oxygen species (ROS) upon confrontation culture and was totally abolished in the presence of the free radical scavenger vitamin E. Incubation of embryoid bodies with baicalein, epicatechin, berberine, and acteoside, which are herbal ingredients used in traditional Chinese medicine, significantly inhibited angiogenesis in embryoid bodies and decreased intracellular ROS levels. Tumor-induced angiogenesis in confrontation cultures was totally abolished in the presence of the free radical scavenger vitamin E. Because herbal ingredients down-regulated MMP expression, we conclude that ROS generated during confrontation culture induce the expression of MMPs that are necessary for endothelial cell invasion into the tumor tissue.     

Specific enzymatic treatment of bovine and human articular cartilage: implications for integrative cartilage repair

OBJECTIVE: Chondrocyte death in articular cartilage wound edges and the subsequent lack of matrix-producing cells in the interface area are considered to be a major cause of impaired cartilage wound healing and poor integrative cartilage repair. This study was undertaken to investigate whether enzymatic matrix digestion can be used to stimulate integrative cartilage repair via a mechanism of local increase in the amount of vital chondrocytes in cartilage wound edges. METHODS: Full-thickness bovine articular cartilage samples were cultured in vitro for 14 days in standard medium. Samples were either left untreated or treated for 48 hours with 0.3% hyaluronidase or 30 units/ml highly purified collagenase VII. Nuclear and cytoplasmic changes were analyzed to determine cell viability, and the number of vital chondrocytes in wound edges was determined. Subsequently, we investigated whether increased chondrocyte density in the lesion edges resulted in better wound healing. Finally, full-thickness human tibial plateau cartilage explants were tested with similar enzyme treatment protocols to determine the clinical value of our results. RESULTS: In bovine explants a rapid onset of chondrocyte death was observed in wound edges in all treatment groups. This led to low chondrocyte density in a band of 0-150 microm from the lesion edges in untreated and hyaluronidase-treated explants. Treatment with 30 units/ml collagenase resulted in a significant increase in chondrocyte density in this area. The integration experiments demonstrated improved integration of the lesion edges after treatment with collagenase. In human articular cartilage an increase in chondrocyte density at the lesion edges could also be achieved, but only when proteoglycans were depleted from the wound edges prior to collagenase treatment. CONCLUSION: Treatment with highly purified collagenase improves integrative cartilage repair, possibly by increasing the cell density at cartilage wound edges.     

Adenosine in myocardial protection in on-pump and off-pump cardiac surgery

Adenosine is most well known for its potent vasodilation of the vasculature. However, it also promotes glycolysis, and activates potassium-sensitive adenosine triphosphate (K(ATP)) channels. Adenosine also strongly inhibits neutrophil function such as superoxide anion production, protease release, and adherence to coronary endothelial cells. Hence adenosine attenuates ischemic injury as well as neutrophil-mediated reperfusion injury. Adenosine has also been implicated in the cardioprotective phenomenon of ischemic preconditioning. Accordingly experimental evidence shows that adenosine reduces postischemic injury when administered before ischemia and at the onset of reperfusion. Clinical studies in cardiology and cardiac surgery show cardioprotective trends with adenosine treatment but the effects are not as dramatic as those reported by experimental studies.     

Treating type 2 diabetes in renal insufficiency: the role of pioglitazone

The advent of new antidiabetic drugs is of special importance for diabetic patients with already impaired renal function since renal insufficiency is a relative or absolute contraindication for several of the established hypoglycemic drugs. Pioglitazone is a novel oral hypoglycemic agent that increases insulin responsiveness in target tissues. Pioglitazone and its active metabolites are excreted mainly via the liver. Drug exposure remains almost constant across a wide range of renal function since there is no accumulation of the drug or its active metabolites during repeated dosing in renal insufficiency. The pharmacokinetic properties of pioglitazone are ideally suited for patients with renal insufficiency. Although there are possible side effects (mainly fluid retention and weight gain and--very rarely--hepatotoxicity). Pioglitazone has a good safety profile in diabetic patients with impaired renal function.     

Determination of optic cup depth by confocal scanning laser tomography

PURPOSE: To assess whether confocal scanning laser tomography of the optic disc and clinical ophthalmoscopy using stereoscopic optic disc photographs, agree in the evaluation of the deepest part of the optic cup. PATIENTS AND METHODS: The study included 33 eyes of patients with focal normal-pressure glaucoma. Using 15 degrees color stereoscopic optic disc photographs and dividing the optic disc into an upper and a lower half, two trained observers independently established the location of the deepest part of the cup. By selection, the two observers had made congruent judgements for all eyes in the study. All patients also underwent confocal scanning laser tomography of the optic disc using the Heidelberg Retina Tomograph (HRT). The location of the deepest "mean cup depth" was noted. RESULTS: The deepest optic cup region based on stereoscopic evaluation of photographs and on scanning laser tomography did not correlate significantly with each other (p=0.18; chi-square test, linear-by-linear association). According to the scanning laser tomography data, the maximal optic cup depths were not correlated with the corresponding locations of maximal visual field defect (p=0.80). Using the stereo photographic data, the locations of maximal optic cup depth and maximal visual field defect were correlated (p=0.006). CONCLUSIONS: In some glaucomatous eyes, confocal scanning laser tomographic assessment of the location of the deepest optic cup region does not agree with clinical judgement and, in contrast to clinical examination, does not correlate with the location of the maximal visual field defect.     

Ocular findings in cerebro-oculo-facial-skeletal syndrome (Pena-Shokeir-II syndrome)

PURPOSE: To report the ocular findings in cerebro-oculo-facial-skeletal syndrome or Pena-Shokeir-II syndrome. METHODS: Case report. RESULTS: A five-month-old male infant presented with bilateral posterior polar cataract, microphthalmos, nystagmus, and marked non-glaucomatous optic nerve atrophy. Systemic abnormalities such as microcephaly, micrognathia, flexion contractures of the elbows and knees, hypotonic musculature, and failure to thrive, with pronounced statomotor retardation, led to the diagnosis of cerebro-oculo-facial-skeletal syndrome or Pena-Shokeir-II syndrome. Cataract surgery did not improve the poor visual performance. CONCLUSIONS: Cerebro-oculo-facial-skeletal syndrome (Pena-Shokeir-II syndrome) should be included in the differential diagnosis of bilateral microphthalmos, congenital cataract, nystagmus, and pronounced optic nerve atrophy, and cataract surgery does not markedly improve vision.     

Blood cardioplegia supplementation with the sodium-hydrogen ion exchange inhibitor cariporide to attenuate infarct size and coronary artery endothelial dysfunction after severe regional ischemia in a canine model

BACKGROUND: Activation of the sodium-hydrogen ion exchange mechanism results in accumulation of intracellular calcium through the sodium-calcium ion antiport mechanism. Administration of a sodium-hydrogen ion exchange inhibitor before or during ischemia attenuates myocardial ischemia and reperfusion injury. However, the cardioprotection exerted by sodium-hydrogen ion exchange inhibitors as adjuncts to cardioplegia without perioperative administration has not been tested in a model of surgical reperfusion of acute coronary occlusion with cardiopulmonary bypass. This study tested the hypothesis that sodium-hydrogen ion exchange inhibitor-supplemented blood cardioplegia would reduce postcardioplegia injury after severe regional ischemia. METHODS: In anesthetized open-chest dogs, the left anterior descending coronary artery was occluded for 75 minutes, after which total cardiopulmonary bypass was initiated. After crossclamping, cold (4 degrees C) antegrade blood cardioplegia was delivered every 20 minutes for a total of 60 minutes of cardioplegic arrest. In 8 dogs, the blood cardioplegic solution was unsupplemented (vehicle group), whereas in 8 others the solution was supplemented with the sodium-hydrogen ion exchange inhibitor cariporide (10 micro mol/L, cariporide group). RESULTS: In the in vitro studies, the direct effects of cariporide on neutrophil function were determined. Isolated canine neutrophils were stimulated by platelet activating factor. Cariporide attenuated superoxide anion production in a concentration-dependent manner, with no appreciable effect at 10 micro mol/L (the concentration used in blood cardioplegia) and a peak effect at 100 micro mol/L. In the in vivo cardiopulmonary bypass model, infarct size was significantly (P <.05) smaller in the cariporide group than in the vehicle group (22.4% +/- 3.5% vs 40.1% +/- 5.1% of area at risk), although there were no group differences in postischemic regional wall motion after 2 hours of reperfusion (0.1% +/- 0.9% vs -0.2% +/- 0.3% systolic shortening). Transmural myocardial edema in the area at risk was significantly decreased in the cariporide group (80.6% +/- 0.5%) relative to the vehicle group (83.1% +/- 0.6%). Myeloperoxidase activity in the area at risk, an index of neutrophil accumulation, was significantly lower in the cariporide group than in the vehicle group (4.7 +/- 0.9 absorbence units/[min. g tissue] vs 10.3 +/- 2.3 absorbence units/[min. g tissue]). In isolated postischemic left anterior descending coronary artery rings, maximum relaxation in response to the endothelium-dependent vasodilator acetylcholine was significantly greater in the cariporide group than in the vehicle group (77.5% +/- 7.4% vs 51.4% +/- 8.0%), whereas smooth muscle relaxation in response to nitroprusside was comparable between groups. CONCLUSION: In this canine model, supplementation of blood cardioplegia with cariporide, a sodium-hydrogen ion exchange inhibitor, reduced infarct size, attenuated neutrophil accumulation in the area at risk, and reduced postischemic coronary artery endothelial dysfunction without directly inhibiting neutrophil activity. Cariporide as an adjunct to blood cardioplegia without perioperative administration attenuated surgical ischemia-reperfusion injury in jeopardized myocardium.     

Central retinal vessel trunk exit and location of glaucomatous parapapillary atrophy in glaucoma

OBJECTIVE: To evaluate whether the position of the central retinal vessel trunk exit on the lamina cribrosa spatially correlates with the location of parapapillary atrophy in glaucoma. DESIGN: Clinic-based, observational, cross-sectional study. PATIENTS: Color stereo optic disc photographs of 95 patients with primary or secondary open-angle glaucoma and 65 healthy persons were morphometrically evaluated. The intrapapillary and parapapillary region was divided into four quadrants. We determined the position of the central retinal vessel trunk exit on the lamina cribrosa surface and measured the area of parapapillary atrophy and neuroretinal rim in the four quadrants. MAIN OUTCOME MEASURES: The area of neuroretinal rim and parapapillary atrophy and the position of the central retinal vessel trunk exit. RESULTS: Comparing measurements between opposite disc quadrants showed that beta zone of parapapillary atrophy was significantly (P < 0.05) larger and that the neuroretinal rim was significantly smaller when beta zone and neuroretinal rim were measured in the disc quadrant most distant to the central retinal vessel trunk exit, than if the beta zone and neuroretinal rim were measured in the quadrant containing the vessel trunk exit. Comparing measurements in the disc quadrants between eyes with different positions of the central retinal vessel trunk exit revealed that, in the respective disc quadrant, the beta zone was significantly larger and the neuroretinal rim was smaller in eyes with the vessel trunk exiting in the opposite disc quadrant than in eyes with the vessel trunk exit located in the respective disc quadrant where the measurements were obtained. CONCLUSIONS: Position of the central retinal vessel trunk exit on the lamina cribrosa influences the location of parapapillary atrophy in glaucoma. The longer the distance to the central retinal vessel trunk exit, the more enlarged is parapapillary atrophy and the smaller is the neuroretinal rim. This relationship agrees with the spatial relationship between glaucomatous neuroretinal rim loss and enlarged parapapillary atrophy in glaucoma. Diagnostically, it may indicate that, in eyes with an abnormal configuration of parapapillary atrophy or with an abnormal position of the central retinal vessel trunk exit, early glaucomatous rim changes should be looked for in the disc sector that is most distant to the central retinal vessel trunk exit and where parapapillary atrophy may be relatively large.