Recently, a method to determine the retinal nerve fiber layer (RNFL) attenuation coefficient, based on normalization on the retinal pigment epithelium, was introduced. In contrast to conventional RNFL thickness measures, this novel measure represents a scattering property of the RNFL tissue. In this paper, we compare the RNFL thickness and the RNFL attenuation coefficient on 10 normal and 8 glaucomatous eyes by analyzing the correlation coefficient and the receiver operator curves (ROCs). The thickness and attenuation coefficient showed moderate correlation (r=0.82). Smaller correlation coefficients were found within normal (r=0.55) and glaucomatous (r=0.48) eyes. The full separation between normal and glaucomatous eyes based on the RNFL attenuation coefficient yielded an area under the ROC (AROC) of 1.0. The AROC for the RNFL thickness was 0.9875. No statistically significant difference between the two measures was found by comparing the AROC. RNFL attenuation coefficients may thus replace current RNFL thickness measurements or be combined with it to improve glaucoma diagnosis.

OBJECTIVESTo determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.DESIGNA discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.SETTINGPrimary and secondary care.PARTICIPANTSAdults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).INTERVENTIONSWe compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.MAIN OUTCOME MEASURESGlaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).RESULTSThe best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.LIMITATIONSOptimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.CONCLUSIONSFor confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.FUNDINGThe National Institute for Health Research Health Technology Assessment Programme.

We demonstrate significantly different scattering coefficients of the retinal nerve fiber layer (RNFL) between normal and glaucoma subjects. In clinical care, SD-OCT is routinely used to assess the RNFL thickness for glaucoma management. In this way, the full OCT data set is conveniently reduced to an easy to interpret output, matching results from older (non-OCT) instruments. However, OCT provides more data, such as the signal strength itself, which is due to backscattering in the retinal layers. For quantitative analysis, this signal should be normalized to adjust for local differences in the intensity of the beam that reaches the retina. In this paper, we introduce a model that relates the OCT signal to the attenuation coefficient of the tissue. The average RNFL signal (within an A-line) was then normalized based on the observed RPE signal, resulting in normalized RNFL attenuation coefficient maps. These maps showed local defects matching those found in thickness data. The average (normalized) RNFL attenuation coefficient of a fixed band around the optic nerve head was significantly lower in glaucomatous eyes than in normal eyes (3.0mm(-1) vs. 4.9mm(-1), P<0.01, Mann-Whitney test).

Chronic stress has been known to cause numerous changes in brain structure that include alter its neurochemistry, excitability, neuronal morphology and cell death (Conrad, 2006). Oxidative stress and reactive oxygen species are known to play a crucial role in the progression of stressinduced neurological diseases (Kontos and Wei, 1986). Production of free radicals after chronic unpredictable stress plays a key role in the pathogenesis of cognitive deficits (Farooq et al., 2012). Traumatic brain injury releases pro-inflammatory cytokines and results into neuroinflammation in hippocampus and other brain parts, leading to cognitive imbalance (Kontos and Wei, 1986). Oxidative damage and apoptosis are two crucial mechanisms that play a significant role in traumatic brain injury-induced neurological disorders (Bayir et al., 2003). Chronic stress is also known to increase serum corticosterone level and impairs memory retrieval process (Kurukulasuriya et al., 2004). Olfactory bulbectomy alters neurogenesis in several regions of brain, which is one of the putative pathogenic mechanisms to explain depression like state (Koo et al., 2010). The several neurodegenerative diseases associated with chronic stress mostly includes depression and memory dysfunction (Radley et al., 2004). All these forms of chronic stress are known to cause oxidative damage, mitochondrial dysfunction, neuroinflammation, and apoptosis with significant alterations in behaviour parameters (Halliwell, 2006). However, the molecular and cellular mechanism and pathways associated with these stress related problems are still not known and poorly understood.