Bulbar Redness and Dry Eye Disease: Comparison of a Validated Subjective Grading Scale and an Objective Automated Method.

SIGNIFICANCE: In this study, assessments of conjunctival redness were performed to evaluate whether patients with or without dry eye disease (DED) could be discriminated based on this measure. Our findings suggest that subjectively grading redness by quadrant, as opposed to automated en face measurements, may be more suitable for this purpose. PURPOSE: This study aimed to quantify bulbar redness using the validated bulbar redness (VBR) grading scale and an automated objective method (Oculus Keratograph 5M; K5M) in participants with DED and non-DED controls. METHODS: Participants with DED (Ocular Surface Disease Index score ≥20 and Oxford scale corneal staining ≥2) and controls (Ocular Surface Disease Index score ≤10 and corneal staining ≤1) attended two study visits. In part 1A of visit 1, baseline bulbar redness was graded with the VBR scale in each conjunctival quadrant of both eyes, followed by automated measurements of temporal and nasal redness with the K5M. This was immediately followed by part 1B, during which a topical vasoconstrictor was instilled into both eyes. Redness assessments were repeated 5 and 30 minutes after instillation with both instruments. Participants returned 14 days later for visit 2, where the same assessments as for visit 1A were repeated. RESULTS: Seventy-four participants (50 DED and 24 controls) completed the study. There were statistically significant differences in redness between the DED and control groups when assessed with the VBR scale (14/16 comparisons; all, P < .05), whereas no significant differences in K5M-derived redness between the DED and non-DED groups were found at any location or time point. Both subjective and objective instruments detected statistically significant reductions in redness 5 and 30 minutes after instillation of the vasoconstrictor (all, P < .01). CONCLUSIONS: Although both subjective and objective instruments were sensitive to detecting changes in redness induced by vasoconstriction, statistically significant differences in redness between DED and control groups were only found using the VBR scale.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

INTRODUCTION: Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. METHODS: We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 µg, with dose doubling at each step). RESULTS: We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. CONCLUSION: This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Hyperemia Analysis Software for Assessment of Conjunctival Hyperemia Severity.

PURPOSE: We developed a hyperemia analysis software, which can quantitatively assess the degree of conjunctival hyperemia, and evaluated the reproducibility and reliability of its percent coverage. In addition, we compared the clinical grading and the percent coverage to examine the applicability of the software analysis. METHODS: We took images of the temporal conjunctiva with slit lamp microscopes. We used our hyperemia analysis software to detect blood vessels in the region of interest using its image processing capabilities and obtained a ratio of the area occupied by blood vessels to the rest of the area. In addition, we used the clinical evaluation criteria of the Japanese guidelines for allergic conjunctival diseases 2017 to clinically grade the hyperemia in each eye. Nine evaluators examined the images and graded the severity of hyperemia into four stages. We looked for a statistical correlation between the results of the hyperemia analysis software and the clinical grading. RESULTS: The percent coverage of the blood vessels in the region of interest calculated by the hyperemia analysis software correlated with the arithmetic average of our clinical grading (r = 0.953; 95% CI, 0.8470340-0.9862136). CONCLUSION: The percent coverage from our hyperemia analysis software reflects the clinical grading score, suggesting that our software can be used to obtain a detailed analysis of conjunctival hyperemia.

Clinical Severity Classification using Automated Conjunctival Hyperemia Analysis Software in Patients with Superior Limbic Keratoconjunctivitis.

PURPOSE: Digitization of clinical observation is necessary for assessing the severity of superior limbic keratoconjunctivitis (SLK). This study aimed to use a novel quantitative marker to examine hyperemia in patients with SLK. MATERIALS AND METHODS: We included six eyes of six patients with both dry eye disease and SLK (SLK group) and eight eyes of eight patients with Sjögren syndrome (SS group). We simultaneously obtained the objective finding scores by using slit-lamp examination and calculated the superior hyperemia index (SHI) with an automated conjunctival hyperemia analysis software by using photographs of the anterior segment. Three objective finding scores, including papillary formation of the superior palpebral conjunctiva, superior limbal hyperemia and swelling, and superior corneal epitheliopathy, were determined. The SHI was calculated as the superior/temporal ratio of bulbar conjunctival hyperemia by using the software. Fisher's exact test was used to compare a high SHI (≥1.07) ratio between the SLK and SS groups. P-Values < 0.05 were considered statistically significant. RESULTS: The SHI (mean ± standard deviation) in the SLK and SS groups was 1.19 ± 0.50 and 0.69 ± 0.24, respectively. The number of patients with a high SHI (≥1.07) was significantly higher in the SLK group than in the SS group (p < 0.05). The sensitivity and specificity of the SHI in the differential diagnosis between SS and SLK were 66.7% and 87.5%, respectively. An analysis of the association between the objective finding scores and SHI showed that the SHI had a tendency to indicate the severity of superior limbal hyperemia and swelling score in the SLK group. CONCLUSION: The SHI calculated using the automated conjunctival hyperemia analysis software could successfully quantify superior bulbar conjunctival hyperemia and may be a useful tool for the differential diagnosis between SS and SLK and for the quantitative follow-up of patients with SLK.

The measurement of bulbar hyperemia: challenges and pitfalls.

PURPOSE: To review methods of assessing bulbar redness, particularly with respect to the practicality of comparing different rating systems. METHODS: The published literature was reviewed and discussed by a panel of experts and a narrative review prepared. RESULTS: Bulbar hyperemia is a common clinical sign and an important indicator of ocular disease. As bulbar hyperemia is a frequent side effect of topical glaucoma medications, accurate objective measurement is important to allow comparison of clinical studies. A number of different measurement systems have evolved to allow quantification of subjectively assessed redness to be rendered into a form that allows between-treatment comparisons and longitudinal changes in both clinical research and practice. Whereas widespread use of image-based rating scales has improved the assessment of bulbar redness in clinical practice and clinical research, these techniques are less than ideal. The scales are subject to an intrinsic subjectivity and are suboptimal in differentiating the physiologic phenomenon of bulbar hyperemia. There is also a degree of interobserver and intraobserver variation; in some studies, average variation in scores exceed half the extent of the whole scale. Moreover, a lack of interscale validation has led to confusion in comparing the results from clinical studies that use different scales. In a recent series of studies, cross-calibration between the various scales in use has been attempted. CONCLUSIONS: Whereas naive comparisons between the results obtained in studies using different bulbar redness scales can lead to erroneous conclusions, the tools exist to permit meaningful comparisons between rating systems and scales.

Quantitative conjunctival provocation test for controlled clinical trials.

BACKGROUND: The conjunctival provocation test (CPT) is a diagnostic procedure for the assessment of allergic diseases. Photographs are taken before and after provocation increasing the redness of the conjunctiva due to hyperemia. OBJECTIVE: We propose and evaluate an automatic image processing pipeline for objective and quantitative CPT. METHOD: After scale normalization based on intrinsic image features, the conjunctiva region of interest (ROI) is segmented combining thresholding, edge detection and Hough transform. Redness of the ROI is measured from 0 to 1 by the average pixel redness, which is defined by truncated projection in HSV space. In total, 92 images from an observational diagnostic study are processed for evaluation. The database contains images from two visits for assessment of the test-retest reliability (46 images per visit). RESULT: All images were successfully processed by the algorithm. The relative redness increment correlates between the two visits with Pearson's r = 0.672 (p < .001). Linear correlation of the automatic measure is larger than the manual measure (r = 0.59). This indicates a higher reproducibility and stability of the automatic method. CONCLUSION: We presented a robust and effective way to objectify CPT. The algorithm operates on low resolution, is fast and requires no manual input. Quantitative CPT measures can now be established as surrogate endpoint in controlled clinical trials.

The conversion of bulbar redness grades using psychophysical scaling.

PURPOSE: To use psychophysical scaling to investigate if the inclusion of reference anchors affected the perceived redness of the reference images of four bulbar redness grading scales and to convert grades between scales. METHODS: Ten participants were asked to arrange printed copies of the McMonnies/Chapman-Davies (6), IER (4), and Efron (5) grading scale images relative to each other, using the stationary but unlabeled 10, 30, 50, 70, and 90 reference images of the validated bulbar redness scale as additional anchors within a given 0 (minimum) to 100 (maximum) redness range (anchored scaling). The position of each image was averaged across observers to represent its perceived redness within this range. Anchored scaling data were then compared with data from a previous study, where the images of all four grading scales had been scaled for the same experimental setup, but with no reference anchors provided (non-anchored scaling). Averaged perceived redness as determined with anchored scaling was used to cross-calibrate grades between scales. RESULTS: Overall, perceived redness of the reference images was significantly different within each scale (repeated measures analysis of variance, all scales p < 0.001). There were differences in perceived redness range and when comparing reference levels between scales. Anchored scaling resulted in an apparent shift to lower perceived redness for all but one reference image compared with non-anchored scaling, with the rank order of the 20 images for both procedures remaining fairly constant (Spearman's ρ = 0.99). CONCLUSIONS: The re-scaling of the reference images in the anchored scaling experiment suggests that redness was assessed based on within-scale characteristics and not using absolute redness scores, a mechanism that can be referred to as clinical scale constancy. The perceived redness data allow practitioners to modify the grades of the scale they commonly use for comparison of their grading estimates with grades obtained with another calibrated scale.

The use of fractal analysis and photometry to estimate the accuracy of bulbar redness grading scales.

PURPOSE: To use physical attributes of redness to determine the accuracy of four bulbar redness grading scales, and to cross-calibrate the scales based on these physical measures. METHODS: Two image-processing metrics, fractal dimension (D) and percentage of pixel coverage (% PC), as well as photometric chromaticity were selected as physical measures, to describe and compare grades of bulbar redness among the McMonnies/Chapman-Davies scale, the Efron Scale, the Institute for Eye Research scale, and a validated scale developed at the Centre for Contact Lens Research. Two sets of images were prepared by using image processing: The first included multiple segments covering the largest possible region of interest (ROI) within the bulbar conjunctiva in the original images; the second contained modified scale images that were matched in size and resolution across scales, and a single, equally-sized ROI. To measure photometric chromaticity, the original scale images were displayed on a computer monitor, and multiple conjunctival segments were analyzed. Pearson correlation coefficients between each set of image metrics and the reference image grades were calculated to determine the accuracy of the scales. RESULTS: Correlations were high between reference image grades and all sets of objective metrics (all Pearson's r >or= 0.88, P

Comparison of an objective method of measuring bulbar redness to the use of traditional grading scales.

PURPOSE: The primary objective was to compare measures of bulbar redness objectively using a photometric method with standard grading methods. Measures of redness were made on 24 participants wearing a silicone hydrogel contact lens in one eye for overnight wear. This report compares hyperaemia after 1 week of daily wear (baseline) with redness measured after 6 months of overnight wear. METHOD: A new method of objectively measuring bulbar conjunctival redness was performed using the Spectrascan650 Photometer by Photo Research under fixed illumination. Photometric measures in CIEu(*) chromaticity values involve the measurement of chromaticity, a physical analogue of redness, greenness and blueness in the image. This method was validated in Part 1 of the study using repeated measurements on the photographic CCLRU scale. In Part 2 of the study, the photographic grading scale (CCLRU) from 0 (none) to 100 (extreme) was used to make the comparison. RESULTS: Part 1 indicated that the photometer provides a repeatable and reliable measure of bulbar redness (CCC=0.989). A moderately strong and significant correlation was found between the CIEu(*) chromaticity values and the analogue data (R=0.795, p=0.000) at each measurement session (from baseline to 1 day, 1 week, and 1, 3 and 6 months of overnight wear). CONCLUSIONS: This new standardized and objective method of measuring bulbar redness has great potential to replace subjective grading scales, especially with multi-centre studies, where variability between investigators occurs. This method may also detect smaller changes between visits or between eyes.

The Hampton-Gledhill 2-stage pressure risk-assessment system.

Pressure ulcers are largely preventable and, therefore, patients dying of large, necrotic pressure damage is an unacceptable situation. Lee Gledhill is both a nurse and a barrister and has been involved in many cases involving nurses facing court proceedings when their patients' primary cause of death is pressure ulcers. Sylvie Hampton, has acted as expert witness in some of these cases. It became obvious to the two authors that had healthcare assistants (HCAs) been more aware of how pressure damage could be detected and then prevented, some of the supervising nurses would not have been facing legal charges. The authors decided to produce a simple method of assessing first-stage skin changes for HCAs to not only recognize these changes, but also to have a framework in place describing the actions they need to take. This framework was produced as a card (the Hampton-Gledhill 2-stage pressure risk-assessment system). The card is being validated in many nursing homes and hospitals around the UK and in Jersey.

Characterizing reactive hyperemia via tissue reflectance spectroscopy in response to an ischemic load across gender, age, skin pigmentation and diabetes.

PURPOSE: Pressure ulcers represent a major secondary complication for amputees with diabetes and further complications may arise since ulcers are particularly hard to heal in this population. This study characterized the hyperemic response to a localized ischemic load in people with diabetes and amputation and compared it to that of subjects without diabetes or amputation. SUBJECTS: Case-control study matching subjects by gender, age, skin pigmentation, and smoking status. METHODS: Applying 150 mmHg to the patellar tendon for 10 minutes induced reactive hyperemia (RH). Tissue reflectance spectroscopy measured hemoglobin (HbO(2)) concentration in tissue before, during and after application of pressure. Refill time, Maximum HbO(2), Time@Max HbO(2), RH area and RH half-life characterized the RH response and were analyzed using ANOVA. All values up to a level of p <0.1 are presented. RESULTS: Analysis included responses from 88 subjects. RH magnitude and temporal parameters varied across skin pigmentation; smokers showed a decreased RH magnitude; vasodilator users had greater RH temporal parameters; no evidence of differences were found across disease state or age. CONCLUSION: Decreased RH response in smokers and subjects with dark skin might indicate a reduced ability to recover from ischemia. The lack of difference in RH response between subjects with and without diabetes was consistent with studies using other disability groups and corroborates the theory that RH is locally mediated.

Automated measurement of bulbar redness.

PURPOSE: To examine the relationship between physical image characteristics and the clinical grading of images of conjunctival redness and to develop an accurate and efficient predictor of clinical redness from the measurements of these images. METHODS: Seventy-two clinicians graded the appearance of 30 images of redness on a 100-point sliding scale with three referent images (at 25, 50, and 75 points) through a World Wide Web-based survey. Using software developed in a commercial computer program, each image was quantified in two ways: by the presence of blood vessel edges, based on the Canny edge-detection algorithm, and by a measure of overall redness, quantified by the relative magnitude of the redness component of each red-green-blue (RGB) pixel. Linear and nonlinear regressors and a Bayesian estimator were used to optimally combine the image characteristics to predict the clinical grades. RESULTS: The clinical judgments of the redness images were highly variable: The average grade range for each image was approximately 55 points, more than half the extent of the entire scale. The median clinical grade was chosen as the most reliable measure of "truth." The median grade was predicted by a weighted linear combination of the edgeness and redness features of each image. The strength of the predicted association was r = 0.976, exceeding the strength of association of all but one of the 72 individual clinicians. CONCLUSIONS: Clinical grading of redness images is highly variable. Despite this human variability, easily implemented image-analysis and statistical procedures were able to reliably predict median clinical grades of conjunctival redness.

The repeatability of discrete and continuous anterior segment grading scales.

PURPOSE: To investigate the repeatability of three anterior segment clinical grading scales: 1) verbal descriptors scale (VDS), 2) photographic matching scale (PS), and 3) continuous matching scale (CS). METHODS: Five optometrists graded 30 slides each of 3-9-o'clock staining, bulbar redness, and palpebral conjunctival roughness twice, separated by at least a day. VDS and PS were five-point scales (0-4) with half grades permitted. The CS was a 5-second, 240-frame video movie generated using morphing software. PS and CS grading was done with references presented on a computer screen. RESULTS: Averaged across observers, the test-retest intraclass correlation, correlation coefficient of concordance, and Pearson's r ranged from 0.95 to 0.99 (all p < 0.001). Coefficients of repeatability using CS to grade all three ocular conditions ranged between 0.31 and 0.49. The corresponding PS and VDS coefficients of repeatability ranged between 0.37 and 0.49; PS generally had better repeatability than VDS. CONCLUSIONS: Each of the clinical grading scales was reliable. The coefficients of repeatability showed that bulbar redness and palpebral conjunctival roughness were graded with higher precision using CS.

Endodontic classification.

Clinical and histopathologic findings are mixed in current endodontic classifications. A new system, based on symptomatology, may be more useful in clincial practice. The classifications are vital asymptomatic, hypersensitive dentin, inflamed-reversible, inflamed/dengenerating without area-irreversible, inflamed/degenerating with area-irreversible, necrotic without area, and necrotic with area.