Rate of change in central corneal thickness: a viability indicator for conventional drainage tissues in organ culture.

Organ culture of human anterior segments is a powerful tool for understanding trabecular meshwork biology. However, data from a significant percentage of cultured anterior segments are unusable because tissues fail to meet quality control requirements, such as having adequate trabecular meshwork histology. The purpose of the present study was to evaluate a novel, real time method for assessing the viability of conventional drainage tissues in the human anterior segment perfusion model. Twenty-two human anterior segments were perfusion cultured using standard techniques for one week while measuring outflow facility and central corneal thickness (CCT). After perfusion-fixation, toludine blue-stained histological sections of drainage tissues from all four quadrants of each anterior segment were graded and endothelial cell nuclei from cornea centers were stained with 4',6-diamidino-2-phenylindole and counted. We found that most anterior segments with a stable outflow facility had a CCT that decreased over time, while anterior segments with an unstable outflow facility had CCT measurements that failed to decrease over time (P<0.01). When comparing CCT measurements to histological appearance of outflow tissues, we found that in 11/11 cases, anterior segments with an acceptable histological score had a negative CCT slope (P<0.01). Conversely in 3/4 instances, anterior segments with an unacceptable histological score had a positive CCT slope. Lastly, we observed a significant relationship between CCT measurements and corneal endothelial density (P<0.01). Thus, the simple procedure of measuring CCT during anterior segment perfusion provides a second useful measure to assess the viability of the anterior segment during the perfusion process.

The glaucomas.

Glaucoma is the leading cause of irreversible blindness worldwide. The World Health Organization reported in 1995 that 5.1 million persons were bilaterally blind from glaucoma. Its morbidity and prevalence make it a significant public health problem. Because it is a treatable condition, it is important that medical professionals be familiar with this disease, which in most cases is not associated with signs and symptoms that may alert the patient or the physician of its presence. Glaucoma is a progressive optic neuropathy that leads to blindness if left untreated. Risk factors include elevated intraocular pressure, advanced age, African ancestry and positive family history. Several types of glaucomas have been described: acute and chronic, secondary and primary. Primary (Chronic) Open Angle Glaucoma is the most common, with a prevalence in the USA of 1.55%. Blacks are 4 to 5 times more affected than whites. Treatment of glaucoma consists of topical or systemic intraocular pressure lowering agents, laser treatment or surgery. Primary Open Angle Glaucoma is an often-unrecognized disease due to its slow course and lack of symptoms. Because the decline in vision may be slowed but not restored by treatment, it is important that this condition be diagnosed early in its course.

Effect of aging on optic nerve appearance: a longitudinal study.

AIM: To determine whether aging causes detectable changes in the appearance of the optic disc. METHODS: A retrospective longitudinal study was performed with quantitative and qualitative evaluations of digitised stereoscopic optic disc photographs of 224 eyes of 224 subjects. There were three groups: 100 normal subjects from the Framingham Eye Study, 68 glaucomatous patients followed longitudinally, and 56 normal subjects and glaucoma patients who had separate sets of disc photos taken on the same day. A disc was considered qualitatively worse if two of three experienced observers agreed that it was worse. Quantitative progression was defined as a >10% decrease in rim/disc area ratio measured with computer assisted planimetry. RESULTS: With quantitative evaluation, normal eyes (mean follow up 13 years) and same day eyes displayed no statistically significant difference in change of rim/disc area ratios (p=0.095), nor in the number of discs that progressed-five of 100 (5%) v two of 56 (4%) respectively. Glaucomatous eyes (mean follow up 9 years) showed a quantitative loss of disc rim in 24 of 68 (35%), and differed significantly from the normal eyes both in the change of rim/disc area ratio (p<0.0005) and number of discs that progressed (p<0.0005). With qualitative evaluation, the number of progressive discs in the glaucomatous eyes (31%) differed significantly (p<0. 0005) from the normal eyes (3%) and the same day eyes (0%). CONCLUSIONS: Over a period of follow up appropriate for long term outcome studies in glaucoma, there was no quantitatively or qualitatively detectable neuroretinal rim loss in normal aging optic nerves with stereoscopic optic disc photographs.

Comparison of methods to detect visual field progression in glaucoma .

OBJECTIVE: The purpose of the study is to develop alternative statistical approaches for evaluating the trend of visual field series over time and to compare the results to human observers. DESIGN: Retrospective analysis of visual field results. PARTICIPANTS: Eighty-three eyes of 83 patients (phakic or pseudophakic) with open-angle glaucoma and 5 or more eligible fields were included in the study. INTERVENTION: Three experienced observers independently reviewed the field series to determine stability or progression. MAIN OUTCOME MEASURES: The following additional methods to determine progression of visual field loss were used: (1) pointwise univariate regression analysis and a glaucoma change analysis; (2) univariate regression analysis on visual field indices mean deviation, corrected loss variance, and glaucoma pattern index; (3) pointwise multivariate regression analysis with fixed effects on panel data; and (4) clusterwise multivariate regression analysis with fixed effects on panel data. The results of different statistical methods were compared by determining the pairwise agreement (Cohen's weighted kappa) between each technique and three experienced observers. RESULTS: Patients were observed for a mean (+/-standard deviation) of 5.6 (+/-1.4) years. The visual fields of 27 (33%) and 56 (67%) eyes were considered to have progressed or remained stable, respectively, based on agreement of at least 2 of 3 observers. Univariate regression analysis on visual field indices was not useful for detection of visual field progression. Pointwise and clusterwise regression analyses with fixed effects on panel data performed as well as pointwise univariate regression analysis compared with human observers (kappa = 0.52, 0.53, and 0.55, respectively). Both methods showed better agreement with human observers than with glaucoma change analysis (kappa = 0.41). CONCLUSIONS: A new statistical model, multivariate regression analyses with fixed effects on panel data, is an appropriate method to evaluate the course of visual field series over time and shows reasonable agreement with experienced observers and pointwise univariate regression analysis.

Automatic detection of glaucomatous visual field progression with neural networks.

OBJECTIVE: To evaluate computerized neural networks to determine visual field progression in patients with glaucoma. METHODS: Two hundred thirty-three series of Octopus G1 visual fields of 181 patients with glaucoma were collected. Each series was composed of 4 or more reliable visual fields from patients who had previously undergone automated perimetry. The visual fields were independently evaluated in a masked fashion by 3 experienced observers (K.N.-M, M.W., and J.C.) and were judged to show progression based on the agreement of 2 observers. The stable and progressed series were matched for mean defect at baseline. The threshold data were submitted to a back propagation neural network that was trained to classify each series as stable or progressed. Two thirds of the data were used for the training and the remaining one third to test the performance of the network. This was repeated 3 times to classify all of the series (changing the training and test series). RESULTS: Fifty-nine series of visual fields showed progression and 151 were judged stable. Neural network sensitivity was 73% and specificity was 88% (threshold for progression = 0.5). The concordance of the neural network with the observers was good (0.50 < or = kappa > or = 0.64). CONCLUSIONS: A neural network can be trained to recognize visual field progression in good concordance with experienced observers. Neural networks may be used to aid the physician in the evaluation of glaucomatous visual field progression.

Detection of structural damage from glaucoma with confocal laser image analysis.

PURPOSE: To determine which structural optic nerve head parameters measured with confocal scanning laser image analysis that best discriminate between normal persons and those with glaucoma. METHODS: One randomly selected eye of 53 patients with early open-angle glaucoma (average visual field mean deviation = -4.8 dB) and of 43 age-, race-, and refractive error-matched normal subjects were studied. The performance of nine structural measures was evaluated with linear multivariate analysis and a neural network: cup area, cup to disc area ratio, rim area, height variation contour, cup volume, rim volume, cup shape measure, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area. A discriminant function was derived with two thirds of the sample and its discriminant power tested on the remaining one third. This was repeated twice so that the entire sample was used for training and testing. A neural network was trained and tested in the same way. Stereoscopic color optic nerve photographs of the same eyes were evaluated qualitatively by three experienced, masked observers. Receiver operating characteristic (ROC) curves of discriminant function, neural network results, and qualitative evaluation were plotted. Comparisons of the areas under the ROC curves were performed with nonparametric statistics. RESULTS: There were statistically significant differences between the normal and glaucoma groups for all measures (P < or = 0.007) except for height variation contour, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area. Cup shape measure provided the single best measure to distinguish between normal subjects and those with early glaucoma and had a diagnostic precision of 84%. Neural network diagnostic precision, when all measures were used, was 92% and decreased to 82% when cup shape measure was omitted. The area under the ROC curve when all measures were combined was 0.94; it was significantly lower (P = 0.04) when cup shape measure was omitted (area = 0.84). The area under the ROC curve for qualitative optic disc evaluation by experienced observers was 0.93. There was no statistically significant difference between qualitative evaluation and neural network performance (P = 0.80). CONCLUSIONS: Cup shape measure, the statistical third moment of the distribution of depth values of the optic nerve head obtained with confocal laser image analysis, can be used to discriminate between normal persons and those with early glaucomatous damage with high diagnostic precision.

Neural networks to identify glaucoma with structural and functional measurements.

PURPOSE: Neural networks can recognize patterns and classify complex variables. We assessed the ability of neural networks to discriminate between normal and glaucomatous eyes by using structural and functional measurements. METHODS: Several neural network algorithms were tested with a database of 185 eyes of patients with early glaucomatous visual field loss (average mean defect, 4.5 dB) and 54 eyes of age-matched normal control subjects. The information used included automated visual field indices (mean defect, corrected loss variance, and short-term fluctuation) and structural data (cup/disk ratio, rim area, cup volume, and nerve fiber layer height) from computerized image analysis. RESULTS: A back propagation network with two intermediate layers assigned an estimated probability of being glaucomatous to each eye and correctly identified 88% of all eyes with 90% sensitivity and 84% specificity. The same neural network trained with only structural data correctly identified 80% of the eyes with 87% sensitivity and 56% specificity, and when trained with functional data only, it correctly identified 84% of the eyes with 84% sensitivity and 86% specificity. CONCLUSION: Analysis of several optic nerve and visual field variables by neural networks can help identify early glaucomatous damage and assign an estimated probability that early damage is present in individual patients.

Correlation between the progression of optic disc and visual field changes in glaucoma.

Visual field test and optic disc evaluation are the standard examination techniques used to detect the onset and progression of glaucoma. This explorative study was performed to assess the temporal correlation between visual field and optic disc changes in eyes with ocular hypertension and well-established glaucoma. Eighty-six hypertensive and 16 glaucomatous eyes were followed up for a period of up to 9 years (average 4.4 yrs) using kinetic and computerized static perimetry and optic disc manual morphometry. Perimetric changes were based on a series of strict criteria and optic disc changes were based as a reduction in the baseline rim area/disc area ratio (R/D) measurement exceeding the 99% confidence interval for intraobserver reproducibility (7.7%). Optic disc changes were found prior to visual field changes in four hypertensive eyes, whereas visual field changes were found prior to disc changes in six glaucomatous eyes (p = 0.042). The results of our explorative study suggest that quantitative optic disc analysis may be more sensitive than visual field examination in detecting early glaucomatous changes, whereas visual field examination may be more sensitive than quantitative optic disc analysis in detecting glaucomatous progressions in eyes with well established glaucoma.

Outcomes of trabeculectomy for primary open-angle glaucoma.

PURPOSE: To determine the long-term functional and structural outcomes in patients treated with trabeculectomy for primary open-angle glaucoma. METHODS: Records of 78 consecutive patients (78 eyes) who had their first trabeculectomy were studied retrospectively (duration of follow-up, 25 to 112 months). Serial automated perimetry and stereoscopic optic disc photographs were used to assess the long-term efficacy of trabeculectomy to prevent progressive glaucomatous damage. Stereoscopic optic disc photographs were available for 29 eyes (38%). Criteria for intraocular pressure control were a minimum intraocular pressure reduction of 20% and intraocular pressure at or below 20 mmHg. RESULTS: There was no evidence of progression of glaucomatous damage in 81% and 65% of the eyes after 3 and 6 years, respectively. The visual field deteriorated in 16 eyes (21%) and progressive structural optic nerve damage occurred in 4 eyes (5%) during follow-up. Deterioration of the optic nerve head in the absence of visual field progression was detected in three (4%) of those eyes. In 19 eyes (25%), further glaucoma surgery was performed. The probability of successful intraocular pressure control after a single operation was 48% and 40% at 3 and 5 years, respectively. CONCLUSION: Progressive glaucomatous damage occurs in about one third of eyes with moderate to severe primary open-angle glaucoma over a 6-year follow-up after trabeculectomy.

Regional test-retest variability of confocal scanning laser tomography.

PURPOSE: To determine the regional differences in the test-retest variability of topographic measurements of the optic nerve head obtained with a confocal scanning laser retina tomograph. METHODS: Three 10-degree topographic images centered on the optic disk of 20 individuals (20 eyes), five normal subjects, seven glaucoma suspects, and eight glaucoma patients, were acquired and averaged. For each eye, the standard deviation of the mean height at each pixel was calculated from the three images and displayed as a gray scale map, which represents regional test-retest variability. The standard deviation of the mean height of the eight surrounding pixels of each pixel was calculated and plotted as a gray scale map, which represents regional steepness. RESULTS: The variability maps and steepness maps showed close correspondence in all eyes. Regions of high steepness had high variability (r = .31; P < .001). The average variability in relatively flat areas (sixth to 15th percentiles for steepness) was 19 microns, whereas steeper areas (81st to 95th percentiles for steepness) had an average variability of 37 microns. The overall mean variability was 28 +/- 7 microns. CONCLUSIONS: The regional variability of topographic measurements made with the confocal scanning laser tomograph correlates with the steepness of the corresponding region and is highest at the edge of the optic disk cup and along vessels. Because of their high test-retest variability, these steep areas may not be the best locations to follow up patients for progressive glaucomatous damage.

Correlation of visual field with scanning confocal laser optic disc measurements in glaucoma.

OBJECTIVE: To evaluate the correlation between structural optic disc measurements that were obtained with a scanning confocal laser tomograph and functional measurements that were obtained with automated static threshold perimetry. DESIGN: Cross-sectional study. SETTING: An American school of medicine. PATIENTS: Forty-six patients (mean +/- SD age, 63 +/- 10 years) with early to moderate glaucoma (average mean deviation +/- SD, -4.8 +/- 6.2 dB). INTERVENTIONS: Automated static threshold perimetry (performed with either the Octopus G1 program, Interzeag, Schlieren, Switzerland, or the Humphrey 24-2 program, Allergan Humphrey, San Leandro, Calif) and confocal optic disc tomography (performed with the Heidelberg Retina Tomograph, Heidelberg [Germany] Engineering GmbH) were performed on one randomly selected eye per patient. MAIN OUTCOME MEASURE: The correlation between the visual field indexes, namely, the mean deviation and corrected pattern SD, and the topographic measurements for the optic disc and nerve fiber layer. RESULTS: A statistically significant correlation was found between the third central moment of the frequency distribution of the depth values for the optic disc structures and the visual field indexes. Pearson correlation coefficients were r = -.65 (P < .0001) and r = .55 (P < .0001) for the mean deviation and corrected pattern SD, respectively. CONCLUSION: The third central moment of the depth distribution for the optic disc measurements is strongly related to the overall shape of the optic disc cup and is a robust indicator of the degree of glaucomatous optic nerve damage.

Reproducibility of retinal nerve fiber layer evaluation by dynamics scanning laser ophthalmoscopy.

Scanning laser ophthalmoscopy is a laser-based image acquisition technique, which greatly improves the quality of the examination of the fundus and the retinal nerve fiber layer. To assess retinal nerve fiber layer imaging by scanning laser ophthalmoscopy and evaluate intra- and interobserver reproducibility in the classification of retinal nerve fiber layer defects, three independent observers evaluated on two separate occasions the videotaped images of 150 eyes of 80 consecutive patients with ocular hypertension or glaucoma. Ophthalmoscopy was performed using argon blue light (488 nm), confocal apertures of 3 to 1 mm, and 40-degree and 20-degree field angles. Of 150 eyes, 20 (13.3%) were excluded from the study because of the poor quality of the images (clinically significant cataract or myopic peripapillary atrophy). The retinal nerve fiber layer was evaluated qualitatively according to a standard classification: normal pattern, slit, wedge, and diffuse defects. Intraobserver reproducibility, evaluated by kappa statistic, was excellent (> or = 0.75): observer A = 0.78 (95% confidence limits, 0.67-0.88); observer B = 0.84 (95% confidence limits, 0.72-0.96); and observer C = 0.79 (95% confidence limits, 0.67-0.91). Interobserver reproducibility was also excellent in all cases: observers A-B = 0.84 (95% confidence limits, 0.71-0.98); observers A-C = 0.76 (95% confidence limits, 0.65-0.87); and observers B-C = 0.80 (95% confidence limits, 0.69-0.92). Kappa values ranged between 0.59 and 0.69 for intraobserver reproducibility and between 0.55 and 0.69 for interobserver reproducibility when using only those eyes in which abnormalities were noted by at least one observer.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between morphometric optic disc parameters, sex and axial length.

Optic disc correlations were evaluated in normal eyes by means of computer-aided morphometry. Two hundred and thirty-five subjects (144 women and 91 men) entered the study. One eye per patient was randomly chosen for statistical analysis. Disc area (P < 0.05) and axial length (P < 0.0001) were statistically different between sexes. There was a correlation between axial length and both disc area (r for females = 0.55, P < 0.00001; r for males = 0.35, P < 0.0007) and refraction (r for females = 0.40, P < 0.00001; r for males = 0.50, P < 0.00001). The main findings of this investigation were that disc area is greater in male than in female eyes (thus clinically confirming the Ishi's and Quigley's previous observations of autopsy eyes) on the basis of axial length difference between the two sexes, and that disc size correlated with axial length. Disagreements in disc measurements reported in previous studies may be caused by differences in the male/female ratios of their samples.

Technical procedures and software for magnification-corrected morphometry of optic disk photography.

In order to obtain a new diagnostic tool for the early diagnosis of glaucoma, we developed a method based on computerized analysis of the optic disk, cup and neuroretinal rim areas. A fundus camera, a personal computer and a graphic tablet are employed. Suitable software was developed for calculating the areas (disk, cup and rim) providing an index, the rim/disk ratio. The method revealed high repeatability and reproducibility. The simplicity and speed of the procedure make this test suitable for routine clinical use in the early diagnosis of glaucoma.

[Follow-up of surgically treated transsexuals: what has changed?]. / Follow up dei transessuali operati: cosa è cambiato?

The surgery for both male and female transsexuals causes great difference in the behavior of operated patients. Then it is very important to analyze the variations of three parameters before and after operation: 1) the presence and the character of sexual feeling and the modality of sexual intercourse; 2) possibility of orgasm; 3) working behavior. The authors present the results of their study on 16 male transsexuals and 4 female transsexuals.

A reference curve for axial bioelectric potentials in rabbit tibia.

A high coefficient of variation is characteristic of the bioelectric potentials recorded from living long bones. As a consequence, the data collected from animal and human experiments are difficult to use in practical ways. A distribution curve for bone bioelectric potentials has been calculated using polynomial regression analysis to process the voltage values recorded on the whole length of rabbit tibiae, with reference electrodes positioned in three different points of the bone. The distribution curve so obtained is presented to fulfill the need for a reference curve for the bioelectric potentials recorded from rabbit tibial surfaces.

Experimental study on bladder wall's strain in vesical function.

The literature is reviewed and the applicability of Laplace's law to the urinary bladder considered as a sphere is critically discussed. Experiments were performed on live rabbits, on isolated bladders and on rubber balloons to study vesical adaptation and response to filling. From the data obtained, the authors propose "strain", rather than tension, as a characteristic quantity of bladder function and indicate the possible application of these experimental results clinically.