Background Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.00...

https://www.nejm.org/doi/pdf/10.1056/NEJM199412013312203

Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

/pdf/methods-for-evaluating-area-wide-and-organisation-based-3g30nwoi4v.pdf

Methods for evaluating area-wide and organisation-based interventions in health and health care: a systematic review.

Background: Vascular endothelial growth factor (VEGF) is an angiogenic protein and vasopermeability factor whose intraocular concentrations are closely correlated with active neovascularization in patients with diabetes mellitus, central retinal vein occlusion, retinopathy of prematurity, and rubeosis iridis. Objective: To determine whether hypoxia could induce expression of VEGF in retinal cells, which then promotes retinal endothelial cell proliferation. Methods: Retinal pigment epithelial cells, pericytes, and microvascular endothelial cells were exposed to hypoxic conditions in vitro, and RNA expression of VEGF was evaluated by Northern blot analysis. The VEGF-specific proliferative potential of the medium was measured by means of retinal endothelial cell growth assays and VEGF-neutralizing VEGF receptor IgG chimeric protein. Results: The VEGF RNA levels increased within 4 hours and reached elevations of threefold to 30-fold after 18 hours of hypoxia (0% to 5% oxygen, 5% carbon dioxide, 90% to 95% nitrogen) in all cell types (.01 Conclusion: Hypoxia increases VEGF expression in retinal cells, which promotes retinal endothelial cell proliferation, suggesting that VEGF plays a major role in mediating intraocular neovascularization resulting from ischemic retinal diseases.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=ophth&articleId=641436&pdfFileName=archopht_113_12_012.pdf

Hypoxic Regulation of Vascular Endothelial Growth Factor in Retinal Cells

Natural History of Central Retinal Vein Occlusion: An Evidence-Based Systematic Review

• We assessed the variability of results in normal subjects of computerized static threshold perimetry of the central 30° field. Variability of measured threshold values was highly dependent on eccentricity. This included variability among individuals, test-to-test variability within individuals, and intratest variability. All values were significantly larger in the midperiphery than centrally. We found that the mean sensitivity decrement with age was eccentricity dependent, so that the age-corrected normal visual field became not only depressed but also steeper with age. Distributions of individual pointwise deviations from the agecorrected normal mean thresholds were significantly nongaussian. The dependency of variability on test point location, the nongaussian distributions of deviations from age-corrected means, and the variability of age-induced sensitivity reduction should all be considered in the interpretation of computerized visual fields, and particularly in the design of statistical programs for field analysis. Programs not considering these factors are likely to result in misleading analyses.

Normal variability of static perimetric threshold values across the central visual field.

Ocular Neovascularization with Retinal Vascular Occlusion-III: Incidence of Ocular Neovascularization with Retinal Vein Occlusion

Sample size determination for case-control studies of chronic disease are often based on the simple 2 X 2 tabular cross-classification of exposure and disease, thereby ignoring stratification which may be considered in the analysis. One consequence of this approach is that the sample size may be inadequate to attain a specified power and size when performing a statistical analysis on J 2 X 2 tables using Cochran's (1954, Biometrics 10, 417-451) statistic or the Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) statistic. A sample size formula is derived from Cochran's statistic and it is compared with the corresponding one derived when the data are treated as unstratified, and also with two other formulas proposed for stratified data analysis. The formula developed yields values slightly higher than one recently proposed by Munoz and Rosner (1984, Biometrics 40, 995-1004), which assumes that both margins of each 2 X 2 table are fixed, while the present study considers only the case-control margin to be fixed.

https://www.jstor.org/stable/pdfplus/2530706.pdf

Sample size for case-control studies using Cochran's statistic

Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes.

One way of judging if a visual field is abnormal, particularly when a patient has unilateral or asymmetric disease, is to compare the suspicious visual field to that of the normal eye. This assumes that in normal individuals the two visual fields are symmetrical. To determine the extent of normal symmetry, the authors examined the central visual fields of both eyes of 20 normal subjects with program 30-2 of the Humphrey perimeter. The inter-ocular sensitivity difference at single pairs of locations ranged from 0 to 9 decibels with large differences occurring most frequently in the upper field. Confidence intervals constructed from this set of normal data predict that asymmetry exceeding 6 decibels should occur in fewer than 1% of test locations and that asymmetry of overall mean sensitivity exceeding 1.4 decibels should occur in fewer than 1% of normal subjects.

/pdf/interocular-differences-of-the-visual-field-in-normal-rg9mtfpeil.pdf

Interocular differences of the visual field in normal subjects.

We examined the in-vitro activity of 12 antibiotics against Gram-negative bacillary isolates from 141 distinct episodes of nosocomial bloodstream infection occurring from July 1984 through November 1986. At least ten strains of each of the seven most frequently encountered species were tested. Relative potency was carefully assessed by extending the concentrations from 0.004 to 64 mg/l in microdilution tests performed in duplicate. We estimated MIC50 and MIC90 and, importantly, calculated 95% confidence intervals (CI95) for MIC90. Against all isolates, ciprofloxacin, the most potent antibiotic, had an MIC50 of 0.03 and an MIC90 of 0.13 (CI95 0.11 to 0.16 mg/l). Norfloxacin and enoxacin had MIC90 of 0.50 and 0.71 mg/l, respectively. Imipenem, ceftazidime, aztreonam, and cefoperazone had MIC90 of 1.0, 2.0, 5.3, and 5.7 mg/l, respectively. Both cefotaxime and ceftriaxone had MIC90 of 16 mg/l (CI95 13-19.7 mg/l). For tobramycin, gentamicin and amikacin, the MIC90 values were 1.4, 5.7, and 8 mg/l, respectively. Against Pseudomonas aeruginosa (n = 26), Serratia marcescens (n = 19), and Klebsiella pneumoniae (n = 26), the CI95s about the MIC90 for ciprofloxacin were 0.31-0.81, 0.07-0.23, and 0.04-0.10 mg/l, respectively. For optimal comparison of antibiotics used to treat hospital-acquired bacteraemias, only clinically significant nosocomial bloodstream isolates should be studied with regard to their antibiotic susceptibilities; the isolates should be unique (only one isolate per episode of bacteraemia occurring over a defined period of time); an adequate number of isolates of a particular species should be studied; MICs should be determined over a wide range of concentrations; and both the MIC90 and the CI95 should be reported.

Patricio B. Rojas

Papers

Ocular Neovascularization with Retinal Vascular Occlusion-III: Incidence of Ocular Neovascularization with Retinal Vein Occlusion

Sample size for case-control studies using Cochran's statistic

Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes.

Interocular differences of the visual field in normal subjects.

In-vitro susceptibility of nosocomial Gram-negative bloodstream pathogens to quinolones and other antibiotics—a statistical approach