What is a typical optic nerve head?

Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

A novel cell-associated protection assay demonstrates the ability of certain antibiotics to protect ocular surface cell lines from subsequent clinical Staphylococcus aureus challenge.

In vivo effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new in vitro method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline (TET), and bacitracin (BAC) to associate with mammalian cells and to protect these cells from destruction by bacteria. Mammalian cell lines were grown to confluence using antibiotic-free medium and then incubated in medium containing a single antibiotic (0 to 512 µg/ml). After incubation, the cells were challenged with Staphylococcus aureus ocular isolates, without antibiotics added to the culture medium. Epithelial cell layer integrity was assessed by gentian violet staining, and the minimum cell layer protective concentration (MCPC) of an antibiotic sufficient to protect the mammalian cells from S. aureus was determined. Staining was also quantified and analyzed. Bacterial viability was determined by culture turbidity and growth on agar plates. Preincubation of Chang and human corneal limbal epithelial cells with AZM, ERY, and TET at ≥64 µg/ml provided protection against AZM-susceptible S. aureus strains, with increasing protection at higher concentrations. TET toxicity was demonstrated at >64 µg/ml, whereas AZM displayed toxicity to one cell line at 512 µg/ml. BAC failed to show consistent protection at any dose, despite bacterial susceptibility to BAC as determined by traditional antibiotic susceptibility testing. A range of antibiotic effectiveness was displayed in this cell association assay, providing data that may be considered in addition to traditional testing when determining therapeutic dosing regimens.

Scan quality effect on glaucoma discrimination by glaucoma imaging devices.

AIM: To evaluate, within ocular imaging scans of acceptable quality as determined by manufacturers' guidelines, the effects of image quality on glaucoma discrimination capabilities. METHODS: One hundred and four healthy and 75 glaucomatous eyes from the Advanced Imaging in Glaucoma Study (AIGS) were imaged with GDx-VCC, HRT II and StratusOCT. Quality score (QS>/=8), pixel standard deviation (SD/=5) were used as quality parameter cut-offs, respectively. GDx nerve fibre indicator (NFI) and HRT Moorfields regression analysis (MRA) classifications and OCT mean retinal nerve fibre layer (RNFL) thickness were used as the discriminatory parameters. Logistic regression models were used to model the dichotomous clinical classification (healthy vs glaucoma) as a function of image-quality parameters and discriminatory parameters. RESULTS: Quality parameter covariates were statistically non-significant for GDx and HRT but had an inverse effect on OCT in predicting disease (a higher SS had a lower probability of glaucoma). Age was a significant covariate for GDx and HRT, but not OCT, while ethnicity and interaction between the image quality and the institute where scans were acquired were significant covariates in the OCT models. CONCLUSION: Scan quality within the range recommended as acceptable by the manufacturer of each imaging device does not affect the glaucoma discriminating ability of GDx or HRT but does affect Stratus OCT glaucoma discrimination.

Retinal nerve fibre layer thickness measurement reproducibility improved with spectral domain optical coherence tomography.

BACKGROUND/AIMS: To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT. METHODS: Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT. RESULTS: CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility. CONCLUSIONS: SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.

The radiographic measurement of ulnar translation.

Our purpose was to quantify the Gilula score for measurement of lunate uncovering, to compare it with another method of measurement and to examine the reliability of these measurements in posteroanterior (PA) views in radial and ulnar deviation. Seventy-six normal wrist arthrograms were reviewed retrospectively. Carpal height and lunate uncovering measurements were made. Statistical analysis included mixed effects models to evaluate the difference between the mean measurements in each position. Reproducibility was assessed using imprecision estimates. Normal values for the Gilula method were 40% lunate uncovering in neutral, 49% in radial and 20% in ulnar deviation. There was a statistically significant difference between the values in the different views. Ulnar translation of the carpus can be measured reliably on neutral and radially deviated PA views using the Gilula method, but the different normal values for each view should be used. The Schuind method of measurement is comparable to the Gilula method in the neutral PA view.