Objective quantification of vitreous haze on optical coherence tomography scans: no evidence for relationship between uveitis and inflammation in multiple sclerosis.

BACKGROUND AND PURPOSE: The occurrence of intermediate uveitis, which is characterized by the presence of vitreous haze (VH), in patients with multiple sclerosis (MS) may be a sign of coexistent inflammatory central nervous system (CNS) disease activity. Using an automated algorithm to quantify VH on optical coherence tomography (OCT) scans, the aim was to investigate whether VH in MS patients is associated with signs of inflammatory CNS disease activity. METHODS: Vitreous haze was quantified on OCT macular volume scans of 290 MS patients and 85 healthy controls (HCs). The relationship between VH and clinical, retinal OCT and magnetic resonance imaging parameters of inflammatory disease activity was investigated using generalized estimating equations. RESULTS: Mean VH scores did not differ between patients and HCs (P = 0.629). Six patients (2.1%) showed values higher than the highest of the controls by HCs. VH scores did not differ between the different disease types or between eyes with and without a history of optic neuritis (P = 0.132). VH was not associated with inner nuclear layer volume on OCT (P = 0.233), cerebral T2 lesion load on magnetic resonance imaging (P = 0.416) or the development of new relapses (P = 0.205). CONCLUSION: In this study, OCT-based automated VH estimation did not detect increased vitreous inflammation in MS patients compared to HCs and did not find an association with CNS inflammatory burden.

Psychological, social and everyday visual impact of diabetic macular oedema and diabetic retinopathy: a systematic review.

AIMS: To synthesize the evidence on the impact of diabetic retinopathy and diabetic macular oedema from the patient perspective. METHODS: A systematic literature review was conducted using MEDLINE Complete, PsycINFO, EMBASE and AMED. We included articles investigating the impact of the condition on quality of life, symptoms, visual functioning, activities of daily living, well-being, social functioning, and financial status. The studies evaluated were observational, including cross-sectional, prospective cohort and retrospective cohort designs. Outcome data were extracted and synthesized. RESULTS: Searches yielded 5114 publications. After screening, 85 studies were included, measuring the following outcomes: visual functioning (n=46); quality of life (n=22); well-being (n=16); functional status (n=5); work (n=4); and visual task performance (n=2). Diabetic retinopathy has a considerable impact on visual functioning and this is greater in people with greater disease severity. Diabetic retinopathy significantly limits activities including working, driving, walking and reading, and has the potential to have a negative impact on psychological well-being. CONCLUSIONS: Diabetic retinopathy is associated with poor self-reported visual functioning, well-being, and health-related quality of life. Ability to perform basic everyday tasks appears to diminish with disease severity. Some studies suggest impaired mobility and problems with work, but there are gaps in this evidence.

Optimizing OCT acquisition parameters for assessments of vitreous haze for application in uveitis.

Detection and evaluation of inflammatory activity in uveitis is essential to the management of the condition, and yet continues to be largely dependent on subjective clinical measures. Optical coherence tomography (OCT) measurement of vitreous activity is an alternative to clinical vitreous haze scoring and has passed a number of early validation studies. In this study we aimed to evaluate the impact of 'operator factors' on the variability of the technique as part of the validation process, and to help evaluate its suitability for 'real world' use. Vitreous haze index was calculated as a ratio between the reflectivity of the vitreous and of the outer retina in each scan. Different scanning conditions were tested and their effect on the measurement is reported. Our results show that the 'quantitative imaging' technique of OCT-measured vitreous activity had good reliability in normal subjects under a range of 'real world' conditions, such as when the operator changes the averaging value. The technique was however vulnerable to highly inaccurate focussing or abnormal downward displacement of the image. OCT-based quantification of vitreous activity is a promising alternative to current subjective clinical estimates, with sufficient 'tolerance' to be used in routine clinical practice as well as clinical trials.

A view on glaucoma--are we seeing it clearly?

Successful clinical management of glaucoma should not simply be about control of intraocular pressure, but must equate to correct decisions about intensifying treatment when patients are at risk of developing 'visual disability'. Yet little is known about what visual field defects, at different stages of glaucoma, specifically affect patients' abilities to perform everyday visual tasks. One way to do this is to measure patient performance in tasks in a lab setting. Another way is to ask patients themselves. The latter can be revealing and demystify views about how patients perceive the world. This short commentary highlights some of the current research in this area.

Are rates of vision loss in patients in English glaucoma clinics slowing down over time? Trends from a decade of data.

PURPOSE: To examine changes in rates of visual field (VF) progression in patients attending a sample of glaucoma clinics in England between 1999 and 2012. METHODS: An archive of 473 252 Humphrey VFs recorded across the UK was retrospectively examined. Distribution of rates recorded in the first half of the decade was compared with the second. The relationship between age and severity of MD loss at baseline with rates of loss and frequency of testing was examined. RESULTS: VF series from 18 926 eyes were analysed. Median rate of MD loss for the period before and after 2003 was -0.11 and -0.06 dB/year, respectively, but the proportion of eyes with medium or fast rates of MD loss remained constant. Median rate of MD loss in older (>70 years) eyes was faster than that observed in younger (<60 years) eyes (-0.21 compared with -0.01 dB/year). Median rate of loss did not vary with severity of MD loss at baseline. Frequency of testing, typically carried out annually, did not vary by age, rate of loss or disease severity. CONCLUSIONS: VFs of eyes treated in the first half of the decade deteriorated more rapidly than those in the second half. Several factors might explain these differences but average effects were small and there was no reduction in the proportion of rapidly progressing eyes over the decade. Older age and, to a lesser extent, worse VF damage at diagnosis are indicators for faster VF loss in clinics, but frequency of VF testing was similar for all patients.

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.

Development of a competency framework for optometrists with a specialist interest in glaucoma.

PURPOSE: To develop a competency framework, using a modified Delphi methodology, for optometrists with a specialist interest in glaucoma, which would provide a basis for training and accreditation. METHODS: A modified iterative Delphi technique was used using a 16-member panel consisting almost exclusively of sub-specialist optometrists and ophthalmologists. The first round involved scoring the relevance of a draft series of competencies using a 9-point Likert scale with a free-text option to modify any competency or suggest additional competencies. The revised framework was subjected to a second round of scoring and free-text comment. The Delphi process was followed by a face-to-face structured workshop to debate and agree the final framework. The version of the framework agreed at the workshop was sent out for a 4-month period of external stakeholder validation. RESULTS: There was a 100% response to round 1 and an 94% response to round 2. All panel members attended the workshop. The final version of the competency framework was validated by a subsequent stakeholder consultation and contained 19 competencies for the diagnosis of glaucoma and 7 further competencies for monitoring and treatment. CONCLUSIONS: Application of a consensus methodology consisting of a modified Delphi technique allowed the development of a competency framework for glaucoma specialisation by optometrists. This will help to shape the development of a speciality curriculum and potentially could be adapted for other healthcare professionals.

A practical approach to measuring the visual field component of fitness to drive.

AIMS: To determine the level of agreement between merged monocular visual field tests (the integrated visual field) and the binocular Esterman visual field test in classifying patients' visual status for UK legal fitness to drive. To examine the link between these two tests and the useful field of view (UFOV) test, a test which is considered to be a surrogate for the visual capability for safe driving. METHODS: Primary open angle glaucoma patients with bilateral overlapping visual field defects were recruited prospectively. Patients performed the bilateral monocular field tests (to generate the integrated visual field), the Esterman test and the UFOV test on the same visit. Patients were classified as "pass" or "fail" by both the integrated visual field and the Esterman test. UFOV risk scores were calculated for each patient. RESULTS: 65 patients were recruited. Substantial agreement was found between the integrated visual field and the Esterman test in classifying patients as "pass" or "fail" (kappa = 0.69). No patients classified as "pass" by the integrated visual field test were classified as "fail" by the Esterman test. Eight patients who were classified as "pass" by the Esterman test were classified as "fail" by the integrated visual field test. The UFOV risk characteristics of these eight patients suggested they were more similar to those of the 13 patients who were classified as "fail" by both the tests, than the 44 patients who were classified as "pass" by both tests. CONCLUSIONS: The integrated visual field test agrees well with the current method (Esterman) of classifying visual fields with regard to legal fitness to drive in the United Kingdom in patients with glaucoma; it appears superior to the current method in identifying those with reduced fitness to drive as measured by the UFOV. The integrated visual field test could perform a valuable screening or diagnostic role in the assessment of glaucoma patients' fitness to drive.

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.

Frequency of testing for detecting visual field progression.

AIMS: To investigate the effect of frequency of testing on the determination of visual field progression using pointwise linear regression (PLR). METHODS: A "virtual eye" was developed to simulate series of sensitivities over time at a given point in the eye. The user can input the actual behaviour of the point (for example, stable or deteriorating steadily), and then a configurable amount of noise is added to produce a realistic series over time. The advantage of this over using patient data is that the actual status of the eye is known. Series were generated using different frequencies of testing, and the diagnosis that would have been made from each series was compared with the true status of the eye. A point was diagnosed as progressing if the regression line for the series showed a deterioration of at least 1 dB per year, significant at the 1% level. From these results, graphs were produced showing the number of points correctly or incorrectly diagnosed as progressing. RESULTS: With the virtual eye deteriorating at a rate of 2 dB/year, it was found that the point was determined to be progressing quicker when more tests were carried out each year. With a stable virtual eye, it was found that increasing the frequency of testing increased the number of series that were falsely labelled as progressing during the first 3 years of testing. CONCLUSIONS: As the frequency of testing increases, the sensitivity of PLR increases. However, the specificity decreases; possibly meaning more unnecessary changes in treatment. Three tests per year provide a good compromise between sensitivity and specificity.

Characteristics of frequency-of-seeing curves for a motion stimulus in glaucoma eyes, glaucoma suspect eyes, and normal eyes.

This study compared frequency-of-seeing curves for a line displacement test in glaucoma patients and normals. Probit analysis of the frequency-of-seeing curves provided the motion thresholds and the slopes of the frequency-of-seeing curves, represented by the interquartile range. The thresholds and interquartile ranges were significantly elevated in the glaucoma eyes and suspect eyes, compared to controls. A logistic regression model incorporating both the interquartile range and threshold significantly improved the sensitivity of the motion test in the suspects. Abnormal shallowing of the slope of the motion frequency-of-seeing curve may represent one of the earliest changes in glaucoma.

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.

Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and LogMAR acuity.

BACKGROUND: A study was carried out to ascertain, in ophthalmologically normal subjects, the short-term effects of dipivefrin hydrochloride 0.1% on visual performance and make comparisons with pilocarpine. METHODS: Twelve normal volunteers aged 20-26 years attended on three occasions. One eye, randomly selected, received one drop of either pilocarpine 2%, dipivefrin or saline 0.9%. High- and low-contrast LogMAR acuity at 6 m and pupil diameter (measured by infra-red pupillometry) were recorded at baseline (T0) and at intervals up to 90 min following instillation of drops. Program 30-2 of the Humphrey Visual Field Analyzer (HFA) was run at T0 and at 60 min after treatment instillation (T60). Saline was always instilled at visit 1, to allow for learning effects. On visits 2 and 3 either pilocarpine or dipivefrin was randomly instilled into the treated eye. RESULTS: Pilocarpine significantly worsened the field global indices mean deviation (P < 0.001) and pattern standard deviation (P < 0.01) compared with T0. There was no significant change with dipivefrin. A significant (P = 0.01) pupil dilation from 5.44 mm (SD 0.79) at T0 to 6.19 mm (SD 1.09) at T90 occurred with dipivefrin. Pilocarpine caused significant miosis. No significant changes in LogMAR values were found with dipivefrin. Pilocarpine significantly (P < 0.01) increased LogMAR values (i.e. reduced acuity) compared with dipivefrin. At T30 the mean increase in LogMAR was 0.76 (SD 0.30) for high and 0.83 (SD 0.11) for low contrast. By T90 recovery of acuity was virtually complete. CONCLUSIONS: In normals dipivefrin causes mydriasis but does not affect the central visual field global indices (as assessed by STATPAC), or high- and low-contrast LogMAR acuity. Pilocarpine adversely affects the visual field and both measures of acuity. Knowledge of these effects is of value in glaucoma therapy and when monitoring the progression of visual loss.

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.

Effect of surgery on visual field progression in normal-tension glaucoma.

PURPOSE: The effect of intraocular pressure-lowering surgery on the rate of visual field progression in normal-tension glaucoma (NTG) was studied. METHODS: Seventeen patients with NTG who underwent trabeculectomy in one eye for worsening visual field loss were included in the first part of the study. All patients had Humphrey 24-2 visual fields at the rate of 2-3 fields per year. Pointwise linear regression analysis of the visual field data was done separately for the preoperative and postoperative periods. This was performed for both operated and fellow eyes. The mean slope (MS), which indicates rate of visual field progression, was calculated. Change in MS was correlated with change in intraocular pressure (IOP). For the second part of the study, 11 patients who had a minimum of 4 visual fields and 18 months of follow-up before surgery were identified. Using the preoperative fields, the rate of sensitivity loss for each visual field location in the operated eye was ascertained for every patient. This rate of loss was extrapolated to generate the expected visual fields, assuming an unchanged rate of progression. The mean sensitivity of the expected visual field was compared with that of the actual field at the last follow-up. RESULTS: The MS in the operated eyes improved from -2.97 +/- 3.21 (mean +/- SD) in the preoperative period to 0.53 +/- 3.83 (P < 0.005; Student's t test) postoperatively. In the fellow eyes the MS changed from -1.78 +/- 2.55 to -1.43 +/- 3.01 (P = 0.754). There was a weak correlation between change in MS and percentage IOP decrease (correlation coefficient 0.39). The difference in mean sensitivity between the expected and actual visual fields was -3.72 dB (P = 0.002), and was better in the actual field. CONCLUSIONS: In this study, surgical lowering of IOP resulted in a slower rate of visual field loss in the operated eye.

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.

Improving the prediction of visual field progression in glaucoma using spatial processing.

PURPOSE: The authors show how the predictive performance of a method for determining glaucomatous progression in a series of visual fields can be improved by first subjecting the data to a spatial processing technique. METHOD: Thirty patients with normal-tension glaucoma, each with at least ten Humphrey fields and 3.5 years of follow-up, were included. A linear regression model of sensitivity against time of follow-up determined rates of change at individual test locations over the first five fields (mean follow-up 1.46 years; standard deviation = 0.08) in each field series. Predictions of sensitivity at each location of the field nearest to 1 and 2 years after the fifth field were generated using these rates of change. Predictive performance was evaluated by the difference between the predicted and measured sensitivity values. The analysis was repeated using the same field data subjected to a spatial filtering technique used in image processing. RESULTS: Using linear modeling of the unprocessed field series, at 1 year after the fifth field, 72% of all predicted values were within +/- 5 dB of the corresponding measured threshold. This prediction precision improved to 83% using the processed data. At the 2-year follow-up field, the predictive performance improved from 56% to 73% with respect to the +/- 5 dB criterion. CONCLUSIONS: Predictions of visual field progression using a pointwise linear model can be improved by spatial processing without increased cost or patient time. These methods have clinical potential for accurately detecting and forecasting visual field deterioration in the follow-up of glaucoma.

Visual field progression: comparison of Humphrey Statpac2 and pointwise linear regression analysis.

BACKGROUND: Humphrey Statpac2 "glaucoma change probability analysis' is a widely available analysis technique to aid the clinician in the diagnosis of glaucomatous visual field deterioration. A comparison of this technique with the more recently described pointwise linear regression analysis (PROGRESSOR) is given. METHODS: Series of visual field data from a group of nine eyes of nine patients with normal-tension glaucoma were selected. Each series had 16 fields with mean follow-up of 5.7 years (SD 0.6 years). Statpac2 "glaucoma change probability analysis' was used to define test locations that had unequivocally deteriorated in the last three fields of each series. The accuracy of both Statpac2 and PROGRESSOR in providing early detection of these deteriorated locations was assessed. RESULTS: The sensitivity and specificity of the two techniques in predicting deteriorated locations were similar when a rate of luminance sensitivity loss of faster than 1 dB/year (2 dB/year for outer locations beyond 15 deg of eccentricity) with a slope significance of P < 0.10 was used as the regression definition of deterioration. The difficulties of comparing two techniques in the early diagnosis of field progression without a true external standard for field loss are illustrated. CONCLUSIONS: PROGRESSOR closely emulates the performance of Statpac2 in detecting sensitivity deterioration at individual test locations. This new technique, which uses all available data in a field series and gives the rate of sensitivity loss at each location, may provide a clinically useful method for detecting field progression in 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.