Objective analysis of toric intraocular lens rotation and centration

PURPOSE: To assess the repeatability of an objective image analysis technique to determine intraocular lens (IOL) rotation and centration. SETTING: Six ophthalmology clinics across Europe. METHODS: One-hundred seven patients implanted with Akreos AO aspheric IOLs with orientation marks were imaged. Image quality was rated by a masked observer. The axis of rotation was determined from a line bisecting the IOL orientation marks. This was normalized for rotation of the eye between visits using the axis bisecting 2 consistent conjunctival vessels or iris features. The center of ovals overlaid to circumscribe the IOL optic edge and the pupil or limbus were compared to determine IOL centration. Intrasession repeatability was assessed in 40 eyes and the variability of repeated analysis examined. RESULTS: Intrasession rotational stability of the IOL was ±0.79 degrees (SD) and centration was ±0.10 mm horizontally and ±0.10 mm vertically. Repeated analysis variability of the same image was ±0.70 degrees for rotation and ±0.20 mm horizontally and ±0.31 mm vertically for centration. Eye rotation (absolute) between visits was 2.23 ± 1.84 degrees (10%>5 degrees rotation) using one set of consistent conjunctival vessels or iris features and 2.03 ± 1.66 degrees (7%>5 degrees rotation) using the average of 2 sets (P =.13). Poorer image quality resulted in larger apparent absolute IOL rotation (r =-0.45,P<.001). CONCLUSIONS: Objective analysis of digital retroillumination images allows sensitive assessment of IOL rotation and centration stability. Eye rotation between images can lead to significant errors if not taken into account. Image quality is important to analysis accuracy.

Mathematical modelling of patient risks in a hospital environment, using multiple regression analysis

The aim of this research work was primarily to examine the relevance of patient parameters, ward structures, procedures and practices, in respect of the potential hazards of wound cross-infection and nasal colonisation with multiple resistant strains of Staphylococcus aureus, which it is thought might provide a useful indication of a patient's general susceptibility to wound infection. Information from a large cross-sectional survey involving 12,000 patients from some 41 hospitals and 375 wards was collected over a five-year period from 1967-72, and its validity checked before any subsequent analysis was carried out. Many environmental factors and procedures which had previously been thought (but never conclusively proved) to have an influence on wound infection or nasal colonisation rates, were assessed, and subsequently dismissed as not being significant, provided that the standard of the current range of practices and procedures is maintained and not allowed to deteriorate. Retrospective analysis revealed that the probability of wound infection was influenced by the patient's age, duration of pre-operative hospitalisation, sex, type of wound, presence and type of drain, number of patients in ward, and other special risk factors, whilst nasal colonisation was found to be influenced by the patient's age, total duration of hospitalisation, sex, antibiotics, proportion of occupied beds in the ward, average distance between bed centres and special risk factors. A multi-variate regression analysis technique was used to develop statistical models, consisting of variable patient and environmental factors which were found to have a significant influence on the risks pertaining to wound infection and nasal colonisation. A relationship between wound infection and nasal colonisation was then established and this led to the development of a more advanced model for predicting wound infections, taking advantage of the additional knowledge of the patient's state of nasal colonisation prior to operation.

Objective analysis of contact lens fit

Purpose: To assess the validity and repeatability of objective compared to subjective contact lens fit analysis. Methods: Thirty-five subjects (aged 22.0. ±. 3.0 years) wore two different soft contact lens designs. Four lens fit variables: centration, horizontal lag, post-blink movement in up-gaze and push-up recovery speed were assessed subjectively (four observers) and objectively from slit-lamp biomicroscopy captured images and video. The analysis was repeated a week later. Results: The average of the four experienced observers was compared to objective measures, but centration, movement on blink, lag and push-up recovery speed all varied significantly between them (p <. 0.001). Horizontal lens centration was on average close to central as assessed both objectively and subjectively (p > 0.05). The 95% confidence interval of subjective repeatability was better than objective assessment (±0.128. mm versus ±0.168. mm, p = 0.417), but utilised only 78% of the objective range. Vertical centration assessed objectively showed a slight inferior decentration (0.371. ±. 0.381. mm) with good inter- and intrasession repeatability (p > 0.05). Movement-on-blink was lower estimated subjectively than measured objectively (0.269. ±. 0.179. mm versus 0.352. ±. 0.355. mm; p = 0.035), but had better repeatability (±0.124. mm versus ±0.314. mm 95% confidence interval) unless correcting for the smaller range (47%). Horizontal lag was lower estimated subjectively (0.562. ±. 0.259. mm) than measured objectively (0.708. ±. 0.374. mm, p <. 0.001), had poorer repeatability (±0.132. mm versus ±0.089. mm 95% confidence interval) and had a smaller range (63%). Subjective categorisation of push-up speed of recovery showed reasonable differentiation relative to objective measurement (p <. 0.001). Conclusions: The objective image analysis allows an accurate, reliable and repeatable assessment of soft contact lens fit characteristics, being a useful tool for research and optimisation of lens fit in clinical practice.

Data analysis methods in optometry Part 7: multiple linear regression

Multiple regression analysis is a complex statistical method with many potential uses. It has also become one of the most abused of all statistical procedures since anyone with a data base and suitable software can carry it out. An investigator should always have a clear hypothesis in mind before carrying out such a procedure and knowledge of the limitations of each aspect of the analysis. In addition, multiple regression is probably best used in an exploratory context, identifying variables that might profitably be examined by more detailed studies. Where there are many variables potentially influencing Y, they are likely to be intercorrelated and to account for relatively small amounts of the variance. Any analysis in which R squared is less than 50% should be suspect as probably not indicating the presence of significant variables. A further problem relates to sample size. It is often stated that the number of subjects or patients must be at least 5-10 times the number of variables included in the study.5 This advice should be taken only as a rough guide but it does indicate that the variables included should be selected with great care as inclusion of an obviously unimportant variable may have a significant impact on the sample size required.

Sensitivity and reliability of objective image analysis compared to subjective grading of bulbar hyperaemia

Aims: To establish the sensitivity and reliability of objective image analysis in direct comparison with subjective grading of bulbar hyperaemia. Methods: Images of the same eyes were captured with a range of bulbar hyperaemia caused by vasodilation. The progression was recorded and 45 images extracted. The images were objectively analysed on 14 occasions using previously validated edge-detection and colour-extraction techniques. They were also graded by 14 eye-care practitioners (ECPs) and 14 non-clinicians (NCb) using the Efron scale. Six ECPs repeated the grading on three separate occasions Results: Subjective grading was only able to differentiate images with differences in grade of 0.70-1.03 Efron units (sensitivity of 0.30-0.53), compared to 0,02-0.09 Efron units with objective techniques (sensitivity of 0.94-0.99). Significant differences were found between ECPs and individual repeats were also inconsistent (p<0.001). Objective analysis was 16x more reliable than subjective analysis. The NCLs used wider ranges of the scale but were more variable than ECPs, implying that training may have an effect on grading. Conclusions: Objective analysis may offer a new gold standard in anterior ocular examination, and should be developed further as a clinical research tool to allow more highly powered analysis, and to enhance the clinical monitoring of anterior eye disease.

Probing three-way interactions in moderated multiple regression:Development and application of a slope difference test

Researchers often use 3-way interactions in moderated multiple regression analysis to test the joint effect of 3 independent variables on a dependent variable. However, further probing of significant interaction terms varies considerably and is sometimes error prone. The authors developed a significance test for slope differences in 3-way interactions and illustrate its importance for testing psychological hypotheses. Monte Carlo simulations revealed that sample size, magnitude of the slope difference, and data reliability affected test power. Application of the test to published data yielded detection of some slope differences that were undetected by alternative probing techniques and led to changes of results and conclusions. The authors conclude by discussing the test's applicability for psychological research. Copyright 2006 by the American Psychological Association.

Statnote 29:discriminant analysis

Discriminant analysis (also known as discriminant function analysis or multiple discriminant analysis) is a multivariate statistical method of testing the degree to which two or more populations may overlap with each other. It was devised independently by several statisticians including Fisher, Mahalanobis, and Hotelling ). The technique has several possible applications in Microbiology. First, in a clinical microbiological setting, if two different infectious diseases were defined by a number of clinical and pathological variables, it may be useful to decide which measurements were the most effective at distinguishing between the two diseases. Second, in an environmental microbiological setting, the technique could be used to study the relationships between different populations, e.g., to what extent do the properties of soils in which the bacterium Azotobacter is found differ from those in which it is absent? Third, the method can be used as a multivariate ‘t’ test , i.e., given a number of related measurements on two groups, the analysis can provide a single test of the hypothesis that the two populations have the same means for all the variables studied. This statnote describes one of the most popular applications of discriminant analysis in identifying the descriptive variables that can distinguish between two populations.

Objective methods for anterior ocular grading

This thesis set out to develop an objective analysis programme that correlates with subjective grades but has improved sensitivity and reliability in its measures so that the possibility of early detection and reliable monitoring of changes in anterior ocular surfaces (bulbar hyperaemia, palpebral redness, palpebral roughness and corneal straining) could be increased. The sensitivity of the program was 20x greater than subjective grading by optometrists. The reliability was found to be optimal (r=1.0) with subjective grading up to 144x more variable (r=0.08). Objective measures were used to create formulae for an overall ‘objective-grade’ (per surface) equivalent to those displayed by the CCLRU or Efron scales. The correlation between the formulated objective verses subjective grades was high, with adjusted r2 up to 0.96. Determination of baseline levels of objective grade were investigated over four age groups (5-85years n= 120) so that in practice a comparison against the ‘normal limits’ could be made. Differences for bulbar hyperaemia were found between the age groups (p<0.001), and also for palpebral redness and roughness (p<0.001). The objective formulae were then applied to the investigation of diurnal variation in order to account for any change that may affect the baseline. Increases in bulbar hyperaemia and palpebral redness were found between examinations in the morning and evening. Correlation factors were recommended. The program was then applied to clinical situations in the form of a contact lens trial and an investigation into iritis and keratoconus where it successfully recognised various surface changes. This programme could become a valuable tool, greatly improving the chances of early detection of anterior ocular abnormalities, and facilitating reliable monitoring of disease progression in clinical as well as research environments.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Correlation between visual function and visual ability in patients with uveitis

Aim: To investigate the correlation between tests of visual function and perceived visual ability recorded with a quality of life questionnaire for patients with uveitis. Methods: 132 patients with various types of uveitis were studied. High (monocular and binocular) and low (binocular) contrast logMAR letter acuities were recorded using a Bailey-Lovie chart. Contrast sensitivity (binocular) was determined using a Pelli-Robson chart. Vision related quality of life was assessed using the Vision Specific Quality of Life (VQOL) questionnaire. Results: VQOL declined with reduced performance on the following tests: binocular high contrast visual acuity (p = 0.0011), high contrast visual acuity of the better eye (p = 0.0012), contrast sensitivity (p = 0.005), binocular low contrast visual acuity (p = 0.0065), and high contrast visual acuity of the worse eye (p = 0.015). Stepwise multiple regression analysis revealed binocular high contrast visual acuity (p <0.01) to be the only visual function adequate to predict VQOL. The age of the patient was also significantly associated with perceived visual ability (p <0.001). Conclusions: Binocular high contrast visual acuity is a good measure of how uveitis patients perform in real life situations. Vision quality of life is worst in younger patients with poor binocular visual acuity.

The effect of corneal thickness and corneal curvature on pneumatonometer measurements

Purpose. The purpose of this study was to investigate the influence of corneal topography and thickness on intraocular pressure (IOP) and pulse amplitude (PA) as measured using the Ocular Blood Flow Analyzer (OBFA) pneumatonometer (Paradigm Medical Industries, Utah, USA). Methods. 47 university students volunteered for this cross-sectional study: mean age 20.4 yrs, range 18 to 28 yrs; 23 male, 24 female. Only the measurements from the right eye of each participant were used. Central corneal thickness and mean corneal radius were measured using Scheimpflug biometry and corneal topographic imaging respectively. IOP and PA measurements were made with the OBFA pneumatonometer. Axial length was measured using A-scan ultrasound, due to its known correlation with these corneal parameters. Stepwise multiple regression analysis was used to identify those components that contributed significant variance to the independent variables of IOP and PA. Results. The mean IOP and PA measurements were 13.1 (SD 3.3) mmHg and 3.0 (SD 1.2) mmHg respectively. IOP measurements made with the OBFA pneumatonometer correlated significantly with central corneal thickness (r = +0.374, p = 0.010), such that a 10 mm change in CCT was equivalent to a 0.30 mmHg change in measured IOP. PA measurements correlated significantly with axial length (part correlate = -0.651, p < 0.001) and mean corneal radius (part correlate = +0.459, p < 0.001) but not corneal thickness. Conclusions. IOP measurements taken with the OBFA pneumatonometer are correlated with corneal thickness, but not axial length or corneal curvature. Conversely, PA measurements are unaffected by corneal thickness, but correlated with axial length and corneal radius. These parameters should be taken into consideration when interpreting IOP and PA measurements made with the OBFA pneumatonometer.

Macular pigment optical density is related to blood glutathione levels in healthy individuals

Purpose. To assess the relationship between macular pigment optical density (MPOD) and blood markers for antioxidant defense in otherwise healthy volunteers. Methods. Forty-seven healthy volunteers were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. The level of MPOD was measured using heterochromatic flicker photometry. Systemic blood pressure (BP) parameters, heart rate (HR), body mass index (BMI), and plasma levels of total, HDL, and LDL cholesterol and triglycerides (TGs) were also determined. Results. A simple correlation model revealed that the level of MPOD correlated significantly and positively with both GSH (P < 0.001) and t-GSH (P < 0.001) levels but not with those of GSSG (P > 0.05). Age, sex, systemic BP parameters, HR, BMI, and plasma levels of cholesterol and TGs did not have any influence on either MPOD or glutathione levels (all P > 0.05). In addition, a forward stepwise multiple regression analysis showed MPOD to have a significantly and independent correlation with GSH levels (ß = 0.63; P < 0.001). Conclusions. In otherwise healthy older individuals, there is a positive correlation between local and systemic antioxidant defense mechanisms.

Alzheimer's disease: the relationship between the density of senile plaques, neurofibrillary tangles and A4 protein in human patients

The numerical density of senile plaques (SP) and neurofibrillary tangles (NFT) as revealed by the Glees silver method was compared with SP and NFT revealed by the Gallyas method and with amyloid (A4) deposits in immunostained sections in 6 elderly cases of Alzheimer's disease. The density of NFT was generally greater and A4 lower in tissue from hippocampus compared with the neocortex suggesting that A4 deposition was less important than the degree of paired helical filament (PHF) related damage in the hippocampus. The density of Glees SP was positively correlated Gallyas SP weakly correlated with A4 deposit number. A stepwise multiple regression analysis which included A4 deposit and Gallyas SP density and accounted for 54% of the variation in Glees SP density. Hence, different populations of SP were revealed by the different staining methods. The results suggested that the Glees method may stain a population of SP in a region of cortex where both amyloid deposition and neurofibrillary changes have occurred.

Beta-amyloid (Abeta) deposits and blood vessels: laminar distribution in the frontal cortex of patients with Alzheimer’s disease

The laminar distribution of diffuse, primitive and classic beta-amyloid (Abeta) deposits and blood vessels was studied in the frontal cortex of patients with Alzheimer’s disease (AD). In most patients, the density of the diffuse and primitive Abeta deposits was greatest in the upper cortical layers and the classic deposits in the deeper cortical layers. The distribution of the larger blood vessels (>10 micron in diameter) was often bimodal with peaks in the upper and deeper cortical layers. The incidence of capillaries (<10 micron) was significantly higher in the deeper cortical layers in most patients. Multiple regression analysis selected vertical distance below the pia mater as the most significant factor correlated with the Abeta deposit density. With the exception of the classic deposits in two patients, there was no evidence that these vertical distributions were related to laminar variations in the incidence of large or small blood vessels.