In vivo oximetry of human bulbar conjunctival and episcleral microvasculature using snapshot multispectral imaging.

Multispectral imaging (MSI) is a well-established technique for non-invasive oximetry of retinal blood vessels, which has contributed to the understanding of a variety of retinal conditions, including glaucoma, diabetes, vessel occlusion, and retinal auto-regulation. We report the first study to use snapshot multi-spectral imaging (SMSI) for oximetry of the bulbar conjunctival and episcleral microvasculature in the anterior segment of the eye. We report the oxygen dynamics of the bulbar conjunctival and episcleral microvasculature at normoxia and at acute mild hypoxia conditions. A retinal-fundus camera fitted with a custom Image-Replicating Imaging Spectrometer was used to image the bulbar conjunctival and episcleral microvasculature in ten healthy human subjects at normoxia (21% Fraction of Inspired Oxygen [FiO2]) and acute mild hypoxia (15% FiO2) conditions. Eyelid closure was used to control oxygen diffusion between ambient air and the sclera surface. Four subjects were imaged for 30 seconds immediately following eyelid opening. Vessel diameter and Optical Density Ratio (ODR: a direct proxy for oxygen saturation) of vessels was computed automatically. Oximetry capability was validated using a simple phantom that mimicked the scleral vasculature. Acute mild hypoxia resulted in a decrease in blood oxygen saturation (SO2) (i.e. an increase in ODR) when compared with normoxia in both bulbar conjunctival (p < 0.001) and episcleral vessels (p = 0.03). Average episcleral diameter increased from 78.9 ± 8.7 µm (mean ± standard deviation) at normoxia to 97.6 ± 14.3 µm at hypoxia (p = 0.02). Diameters of bulbar conjunctival vessels showed no significant change from 80.1 ± 7.6 µm at normoxia to 80.6 ± 7.0 µm at hypoxia (p = 0.89). When exposed to ambient air, hypoxic bulbar conjunctival vessels rapidly reoxygenated due to oxygen diffusion from ambient air. Reoxygenation occured in an exponential manner, and SO2 reached normoxia baseline levels. The average ½ time to full reoxygenation was 3.4 ± 1.4 s. As a consequence of oxygen diffusion, bulbar conjunctival vessels will be highly oxygenated (i.e. close to 100% SO2) when exposed to ambient air. Episcleral vessels were not observed to undergo any significant oxygen diffusion, instead behaving similarly to pulse oximetry measurements. This is the first study to the image oxygen dynamics of bulbar conjunctival and episcleral microvasculature, and consequently, the first study to directly observe the rapid reoxygenation of hypoxic bulbar conjunctival vessels when exposed to ambient air. Oximetry of bulbar conjunctival vessels could potentially provide insight into conditions where oxygen dynamics of the microvasculature are not fully understood, such as diabetes, sickle-cell diseases, and dry-eye syndrome. Oximetry in the bulbar conjunctival and episcleral microvasculature could be complimentary or alternative to retinal oximetry.

Testing food web theory in a large lake: The role of body size in habitat coupling in Lake Michigan.

The landscape theory of food web architecture (LTFWA) describes relationships among body size, trophic position, mobility, and energy channels that serve to couple heterogenous habitats, which in turn promotes long-term system stability. However, empirical tests of the LTFWA are rare and support differs among terrestrial, freshwater, and marine systems. Further, it is unclear whether the theory applies in highly altered ecosystems dominated by introduced species such as the Laurentian Great Lakes. Here, we provide an empirical test of the LTFWA by relating body size, trophic position, and the coupling of different energy channels using stable isotope data from species throughout the Lake Michigan food web. We found that body size was positively related to trophic position, but for a given trophic position, organisms predominately supported by pelagic energy had smaller body sizes than organisms predominately supported by nearshore benthic energy. We also found a hump-shaped trophic relationship in the food web where there is a gradual increase in the coupling of pelagic and nearshore energy channels with larger body sizes as well as higher trophic positions. This highlights the important role of body size and connectivity among habitats in structuring food webs. However, important deviations from expectations are suggestive of how species introductions and other anthropogenic impacts can affect food web structure in large lakes. First, native top predators appear to be flexible couplers that may provide food web resilience, whereas introduced top predators may confer less stability when they specialize on a single energy pathway. Second, some smaller bodied prey fish and invertebrates, in addition to mobile predators, coupled energy from pelagic and nearshore energy channels, which suggests that some prey species may also be important integrators of energy pathways in the system. We conclude that patterns predicted by the LTFWA are present in the face of species introductions and other anthropogenic stressors to a degree, but time-series evaluations are needed to fully understand the mechanisms that promote stability.

Ultrasound reduces the minimum effective local anaesthetic volume compared with peripheral nerve stimulation for interscalene block.

BACKGROUND: Previous studies have demonstrated that lower local anaesthetic (LA) volumes can be used for ultrasound (US)-guided interscalene brachial plexus block (ISB). However, no study has examined whether US can reduce the volume required when compared with nerve stimulation (NS) for ISB. Our aim was to do this by comparing the minimum effective analgesic volumes (MEAVs). METHODS: After ethics approval and informed consent, patients undergoing shoulder surgery were recruited to this randomized, double-blind, up-down sequential allocation study. The volume used for both US and NS was dependent upon the success or failure of the previous block. Success was defined as a verbal rating score of 0/10, 30 min after surgery. Ten needle passes were allowed before defaulting to the opposite group. Patients received general anaesthesia. Pain scores and analgesic consumption were assessed by a blinded observer. Statistical comparisons of continuous variables were performed using Student's t-test and Mann-Whitney U-test as appropriate. Categorical variables were analysed using χ² test. MEAV values were estimated using log-transformed up-down independent pairs analysis and probit regression. Significance was assumed at P<0.05 (two-sided). RESULTS: The MEAV required to provide effective analgesia was significantly (P=0.034) reduced to 0.9 ml [95% confidence interval (CI) 0.3-2.8] in the US group from 5.4 ml (95% CI 3.4-8.6) in the NS group. Fewer needle passes were needed to identify the brachial plexus with US (1 vs 3; P<0.0001) and patients had less pain at 30 min after surgery (P=0.03). CONCLUSIONS: US reduces the number of attempts, LA volume, and postoperative pain when compared with NS for ISB.

Trabeculectomy training in England: are we safe at training? Two year surgical outcomes.

OBJECTIVES: To define the safety profile of trainee trabeculectomy surgery in the United Kingdom. Surgical exposure for trainees in England is limited due to service requirements, the European working time directive constraints and increasing sub-specialisation of glaucoma surgery. Limited knowledge exists on the outcomes of supervised glaucoma surgery. The aim is to determine the safety of supervised trabeculectomy surgery performed by trainee ophthalmologists. METHODS: Retrospective case note review of all patients that had trabeculectomy surgery with MMC by consultant and trainee surgeons across multiple UK centres. All eyes have 2-year follow up. Success was determined using WGA guidelines. Two-tailed p values were obtained using Fisher's exact test to ascertain statistical significance between groups. MAIN OUTCOME MEASURES: intraocular pressure, visual acuity, success and failure rates. RESULTS: 324 eyes were reviewed. 211 (66.4%) cases were performed by glaucoma consultants, 107(33.6%) by trainee ophthalmologists. The majority of eyes in each group were undergoing surgery for POAG. Post-operative IOP control showed no significant difference between consultant and trainee groups at year 1 and year 2. Success rates showed no significant difference between consultant and trainee cases. Failure rates at year 1 showed a significant difference between the two groups. No significant difference was seen at year 2. The trainee group had significantly more complications, when compared with the consultant group. Snellen visual acuity loss was not statistically significant between the two groups at the 2 year time point. CONCLUSIONS: The outcomes of supervised trainee trabeculectomy compare favourably with consultant cases after 2 year follow up. Trainee cases had higher complication rates than consultant cases. Bleb leaks are a common complication of trainee cases, where closer supervision may be required. There is potential for surgical simulation to help increase the success of such cases. These findings may encourage trainee participation in glaucoma surgery.

Severity and stability of glaucoma: patient perception compared with objective measurement.

OBJECTIVE: To elucidate the relationship between the subjective assessment in patients with glaucoma of (1) the severity of their visual loss, and (2) any deterioration in their visual function and their objective visual fields as measured by computed perimetry. DESIGN: First, patients completed a questionnaire relating to perceived visual disability and underwent binocular visual field testing. Second, a separate group of patients answered a question about perceived visual deterioration: their monocular visual field tests were analyzed retrospectively by pointwise linear regression to establish stability or deterioration. SETTING: The Glaucoma Service of a specialist eye hospital, which is a tertiary referral center and serves the local community. SUBJECTS: One hundred twenty-three patients with glaucoma including 62 for the severity arm of the study and 61 for the progression arm. MAIN OUTCOME MEASURES: Questionnaire responses, Esterman binocular disability score, and objective visual field deterioration. RESULTS: Questions strongly associated with Esterman binocular disability scores related to bumping into things, problems with stairs, and finding things that have been dropped. There was a strong association between perceived visual deterioration and measured bilateral visual field deterioration (P<.01). CONCLUSIONS: There is a strong association between some types of perceived visual disability and the severity of binocular field loss. A patient who notices gradual visual deterioration is twice as likely to have bilateral visual field deterioration as not. The findings in this sample of patients with mild-to-moderate glaucoma challenge the belief that glaucoma is an insidious process in which the symptoms do not appear until the end stage of the disease.

Accuracy and implications of a reported family history of glaucoma: experience from the Glaucoma Inheritance Study in Tasmania.

OBJECTIVES: To ascertain the prevalence of previously undiagnosed primary open-angle glaucoma (POAG) within 5 large POAG pedigrees and to evaluate the reliability of a reported family history of glaucoma within these pedigrees. METHODS: The Glaucoma Inheritance Study in Tasmania (GIST) identified several large adult POAG pedigrees. Intraocular pressure (IOP), optic disc stereophotography, and automated perimetry were performed on all adult pedigree members. Participants were classified as normal (IOP <22 mm Hg and normal optic disc and field); glaucoma suspect (normal field, but an IOP >/=22 mm Hg and/or suspicious optic disc); or POAG (field defect and glaucomatous optic disc). Some individuals with POAG had been previously diagnosed by their local ophthalmologist; others were diagnosed as a result of the GIST project. Family members with a prior diagnosis of POAG were asked to report if they were aware of any relatives with POAG. This reported family history was then directly compared with the actual pedigree (before the diagnosis of new cases) to calculate agreement. MAIN OUTCOME MEASURE: The rate of glaucoma in pedigrees and percentage of previously diagnosed glaucoma cases who were aware of the positive family history of POAG. RESULTS: Four hundred forty-two subjects (mean age, 54 years [range, 13-97 years]) from 5 pedigrees were examined: 316 subjects (71%) were normal, 47 (11%) were previously diagnosed with POAG, and 8 (2%) were previously diagnosed glaucoma suspects; 30 cases (7%) of POAG and 41 suspects (9%) were newly diagnosed as a direct result of the GIST examination. Of the 47 previously diagnosed POAG cases, 41 were questioned about their prior knowledge of any family history and 11 (27%) were unaware of their family history of POAG. CONCLUSIONS: Examination of all adult subjects from POAG families yields new cases. Even in large POAG pedigrees, 27% of previously diagnosed POAG patients were unaware of their positive family history. These findings suggest that a higher percentage of adult POAG may be inherited than hitherto reported. Arch Ophthalmol. 2000;118:900-904

Surgery for normal tension glaucoma.

The long term follow up of surgery in normal tension glaucoma is presented. One eye of 18 patients with bilateral progressive disease underwent fistulising surgery. Over follow up periods ranging from 2 to 7 years (50% > or = 5 years) the operated eye showed on average a 30% reduction in intraocular pressure (IOP). This was associated with a marked difference in the rate and number of retinal locations showing a progressive decline in retinal function, suggesting some protective function for lowering IOP in patients with normal tension glaucoma.

Analysis of visual field progression in glaucoma.

BACKGROUND: Despite the widespread use of computerised perimetry the diagnosis of visual field deterioration in following glaucoma patients over time remains particularly difficult. A new method of analysis using a novel graphical display of longitudinal field data is presented. METHODS: A linear regression model of the luminance sensitivity at each stimulus location against time of follow up transforms the quantitative data from a series of fields into a colour coded form which illustrates the spatial configuration of change to aid the interpretation of field loss. The method of analysis and the developed computer software (PROGRESSOR) is described. Comparison with STATPAC-2 glaucoma change probability analysis is given including levels of agreement between the techniques using series of fields of 10 eyes from patients with normal tension glaucoma. RESULTS: Examples of this new method compare well with STATPAC-2 analysis. The level of agreement between the techniques to separate progressing from stable retinal locations is good (kappa = 0.62; SE = 0.04). CONCLUSIONS: This new technique, which combines the change in perimetric sensitivity over time with colour coding of significant change into one image may provide an efficient method to detect true progression in glaucomatous field loss.

High spatial resolution automated perimetry in glaucoma.

BACKGROUND: Automated perimetry is of fundamental importance in assessing visual function in glaucoma. A technique was evaluated to perform high spatial resolution automated perimetry to allow a more detailed assessment of the luminance sensitivity in selected regions of the visual field than is possible with conventional perimetry. METHOD: High spatial resolution perimetry was performed using a Humphrey automated perimeter by measuring luminance sensitivity across a 9 by 9 degree custom grid of 100 test locations with a separation between adjacent locations of 1 degree. Quantitative analysis of the raw and Gaussian filtered thresholds was performed to assess the repeatability of the technique in normals, glaucoma suspects, and glaucoma patients. RESULTS: The testing protocol was well tolerated by all subjects. High spatial resolution perimetry in glaucomatous eyes demonstrated fine luminance sensitivity loss not suspected with conventional perimetry. High spatial resolution perimetry also demonstrated reproducible areas of sensitivity loss in some glaucomatous eyes in areas of the visual field which appear normal with conventional programmes. The repeatability of the technique correlated with mean threshold sensitivity and was substantially improved to clinically acceptable levels by Gaussian filtering the thresholds. CONCLUSION: This technique of high spatial resolution perimetry allows the practical assessment of selected regions of the visual field at higher resolution than conventional perimetry, and may be clinically useful in glaucoma.

Clinical comparison of semiconductor diode versus neodymium: YAG non-contact cyclo photocoagulation.

AIMS: The advent of diode lasers has allowed their use in transscleral cyclo photocoagulation for refractory glaucoma. A trial was performed to compare the ocular hypotensive and inflammatory effects of cyclo photocoagulation using a continuous wave diode (810 nm) and a free running neodymium:yttrium aluminium garnet (Nd:YAG) laser (1064 nm). METHODS: Forty patients with refractory glaucoma were randomised to receive either diode or Nd:YAG therapy. The intraocular pressure (IOP) and inflammatory response to treatment were monitored over 3 months. RESULTS: There was no significant laser related difference in the effect on IOP after one treatment. There was, however, a difference in effect in retreatments with the IOP lowering effect significantly less, but equally sustained in diode retreatment patients. Severe postoperative complications such as hyphaema or fibrinous anterior uveitis only occurred in the Nd:YAG group. CONCLUSION: The degree and duration of the ocular hypotensive response to cyclo photocoagulation appears to be related to the available power output of the system used, and the extent of tissue damage.

Image processing of computerised visual field data.

BACKGROUND: Computerised perimetry is of fundamental importance in assessing visual function. However, visual fields are subject to patient response variability which limits the detection of true visual loss. METHODS: A method of improving the repeatability of visual field data was demonstrated by applying techniques used in image processing. An illustrative sample of nine normals and nine patients with field loss was used. Two successive Humphrey fields were selected for each subject. Repeatability was defined as the standard deviation of the pointwise differences between sensitivity values of the reference field and repeat field. The field data were then separately subjected to Gaussian and median image processing filters and the repeatability was compared with the unprocessed field results. RESULTS: Improvement in repeatability, by a factor of approximately 2, was demonstrated by both processes. CONCLUSION: These techniques may improve the reliable detection of loss of visual function using computerised perimetry.

New approach to estimating variability in visual field data using an image processing technique.

AIMS: A new framework for evaluating pointwise sensitivity variation in computerised visual field data is demonstrated. METHODS: A measure of local spatial variability (LSV) is generated using an image processing technique. Fifty five eyes from a sample of normal and glaucomatous subjects, examined on the Humphrey field analyser (HFA), were used to illustrate the method. RESULTS: Significant correlation between LSV and conventional estimates--namely, HFA pattern standard deviation and short term fluctuation, were found. CONCLUSION: LSV is not dependent on normals' reference data or repeated threshold determinations, thus potentially reducing test time. Also, the illustrated pointwise maps of LSV could provide a method for identifying areas of fluctuation commonly found in early glaucomatous field loss.

Interobserver agreement on visual field progression in glaucoma: a comparison of methods.

AIM: To examine the level of agreement between clinicians in assessing progressive deterioration in visual field series using two different methods of analysis. METHODS: Each visual field series satisfied the following criteria: more than 19 reliable fields, patient age over 40 years, macular threshold at least 30 dB. The first three fields in each series were excluded to minimise learning effects: the following 16 were studied. Five expert clinicians assessed the progression status of each series using both standard Humphrey printouts and pointwise linear regression (PROGRESSOR). The level of agreement between the clinicians was evaluated using a weighted kappa statistic. RESULTS: A total of 432 tests comprising 27 visual field series of 16 tests each were assessed by the clinicians. The level of agreement on progression status between the clinicians was always higher when they used PROGRESSOR (median kappa = 0.59) than when they used Humphrey printouts (median kappa = 0.32). This was statistically significant (p = 0.006, Wilcoxon matched pairs signed rank sum test). CONCLUSIONS: Agreement between expert clinicians about visual field progression status is poor when standard Humphrey printouts are used, even when the field series studied are long and consist solely of reliable fields. Under these ideal conditions, clinicians agree more closely about patients' visual field progression status when using PROGRESSOR than when inspecting series of Humphrey printouts.

Motion detection threshold and field progression in normal tension glaucoma.

Psychophysical tests may demonstrate abnormalities of visual function before the appearance of conventional visual field loss in glaucoma. Motion detection thresholds (MDT) were measured in the normal fellow eye of 51 patients with confirmed normal tension glaucoma and initially unilateral field loss. Humphrey visual fields from the initially normal eye covering a mean follow up of 3.4 years were assessed using pointwise linear regression analysis. In 22 of the 51 eyes with normal visual fields at presentation, field deterioration occurred at one or more Humphrey locations within a mean of 1.7 (SD 1.6) years. An initially abnormal MDT test showed a sensitivity of 73% and a specificity of 90% in predicting field deterioration within the cluster of four Humphrey locations closest to the original MDT test site. Sensitivity was lower (40%) in predicting progression at retinal locations distant from the MDT test site, though specificity remained high (90%).

Simulating binocular visual field status in glaucoma.

AIMS: To simulate the central binocular visual field using results from merged left and right monocular Humphrey fields. To assess the agreement between the simulation and the binocular Humphrey Esterman visual field test (EVFT). METHOD: 59 consecutive patients with bilateral glaucoma each recorded Humphrey 24-2 fields for both eyes and binocular EVFT on the same visit. EVFT results were used to identify patients exhibiting at least one defect (< 10 dB) within the central 20 degrees of the binocular field. This criterion is relevant to a patient's legal fitness to drive in the UK. Individual sensitivity values from monocular fields are merged to generate a simulated central binocular field. Results are displayed as a grey scale and as symbols representing defects at the < 10 dB level. Agreement between patients failing the criterion using the simulation and the EVFT was evaluated. RESULTS: Substantial agreement was observed between the methods in classifying patients with at least one defect (< 10 dB) within the central binocular field (kappa 0.81; SE 0.09). Patients failing this criterion using the EVFT results were identified by the binocular simulation with high levels of sensitivity (100%) and specificity (86%). CONCLUSIONS: Excellent agreement exists between the simulated binocular results and EVFT in classifying glaucomatous patients with central binocular defects. A rapid estimate of a patient's central binocular field and visual functional capacity can be ascertained without extra perimetric examination.

Theoretical perspectives on suicide in gay men with AIDS.

Suicide among gay men with AIDS constitutes a significant theoretical and practical problem. In order to understand this problem it is necessary to consider the specific circumstances that surround these individuals. Whilst there are many theories of suicide with which to address the problem, few are able to capture the special context within which gay men with AIDS live. This article explores three broad concepts from the theoretical literature on suicide that have explanatory potential in this unique context. The three concepts are: the search for meaning in the midst of suffering, Shneidman's [Shneidman, E., 1985. Definition of Suicide. John Wiley, New York] notion of unendurable psychological pain, and hopelessness. This article attempts to demonstrate how these three concepts can incorporate the experiences of gay men with AIDS and contribute to understanding the problem of suicide in this population.

Fine matrix mapping of the macular region in normal subjects.

Using a Humphrey field analyzer and fine matrix mapping, we measured photopic and scotopic thresholds for a blue light stimulus at 100 locations on a 9 degrees by 9 degrees matrix of 1 degree spacing centered at the fovea in 14 normal subjects. Additionally, trial lenses were used to investigate the effect of refractive error. Under photopic conditions the mean sensitivity varied by less than 1 dB over this region. Under scotopic conditions the central values were reduced in sensitivity by 15 dB compared with those at 4 degrees eccentricity. Defocus showed less than 1.2 dB loss with 1.00D of refractive error under photopic condition. The results reflect the properties of rod and cone photoreceptors and the effects of the rod mosaic near the fovea. This technique is a sensitive test of macular visual function.

Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging.

PURPOSE: To determine whether there are differences in retinal vascular oxygen saturation measurements, estimated using a hyperspectral fundus camera, between normal eyes and treated eyes of subjects with asymmetrical primary open-angle glaucoma (POAG). METHODS: A noninvasive hyperspectral fundus camera was used to acquire spectral images of the retina at wavelengths between 556 and 650 nm in 2-nm increments. In total, 14 normal eyes and both eyes of 11 treated POAG subjects were imaged and analyzed using algorithms that use the spectral variation of the optical densities of blood vessels to estimate the oxygen saturation of blood within the retinal vasculature. In the treated POAG group, each of the eyes were categorized, based on the mean deviation of the Humphrey visual-field analyzer result, as either more-advanced or less-advanced, glaucomatous eyes. Unpaired t-tests (two-tailed) with Welch's correction were used to compare the mean oxygen saturation between the normal subjects and the treated POAG subgroups. RESULTS: In less-advanced and more-advanced-treated POAG eyes, mean retinal venular oxygen saturations (48.2±21.6% and 42.6±18.8%, respectively) were significantly higher than in normal eyes (27.9±9.9%; P=0.03 and 0.01, respectively). Arteriolar oxygen saturation was not significantly different between normal eyes and treated POAG eyes. CONCLUSIONS: The increased oxygen saturation of the retinal venules in advanced-treated POAG eyes may indicate reduced metabolic consumption of oxygen in the inner retinal tissues.

Portsmouth visual field database: an audit of glaucoma progression.

AIM: To explore visual field (VF) progression in a cohort of secondary care-treated glaucoma and ocular hypertensive (OHT) patients. METHODS: We extracted VFs from our database drawn from our normal clinical practice. VF series from 4177 eyes from 2208 patients who had five or more VFs were obtained, the 'better' eye was selected and the rate of VF progression was calculated using mean deviation (MD) data. RESULTS: The median rate of progression for the whole sample was -0.1 dB/year (interquartile range (IQR) -4 to 0 dB/year) over a median of 6.7 years (IQR 4.9-8.7). Of 2208 patients, 477 (21.2%) progressed at > -0.5 dB/year; 46 (2.1%) progressed at >-2.0 dB/year. Of those with a 'final MD' of worse than -10 dB (N=244) in their better eye; 14.0% were 'fast progressors' (>-2 dB/year), 33.7% 'moderate progressors' (-1 to -2 dB/year), and 28.8% 'slow progressors' (-0.3 dB to -1 dB/year). Of those with 'initial MD' better than -3 dB and those with worse than -3 dB, 31/1679 (1.8%) and 213/529 (40.3%) respectively, had a final MD of worse than -10 dB. CONCLUSION: Fast progressors, while important, are relatively rare. Moderate and slow progressors make up the majority of the progressing population within this data set. The risk of significant visual loss is much higher in those with initial damage. With increasing life expectancy, moderate and slow progressors may become increasingly clinically important.