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[Pallor of the optic papilla--an early sign of glaucoma. A clinical controlled study of optic disk pallor and papillar cupping in glaucoma simplex, ocular hypertension and normal eyes with the optic nerve head analyzer].

Double examinations of 99 eyes (34 healthy, 12 with ocular hypertension, 53 with primary open-angle glaucoma) were performed with the Optic Nerve Head Analyzer to evaluate whether an increase in disk pallor or in the cup-disk ratio (CDR) is the earlier sign of glaucoma. In eyes with primary open-angle glaucoma the CDR and the mean optic disk pallor value are significantly higher than in healthy eyes. There is no significant difference in the CDR of patients with ocular hypertension as compared to normals. However, the mean pallor value is significantly higher in eyes with ocular hypertension than in healthy eyes. Therefore, an increase in pallor may precede a significant increase in the CDR or detectable visual field defects.

Glaucoma, Open-Angle↗

Pallor as a sign of anaemia in small Tanzanian children at different health care levels.

BACKGROUND: Anaemia is a major complication of Plasmodium falciparum malaria among small children in sub-Saharan Africa. We studied the performance of the Integrated Management of Childhood Illness (IMCI) recommended assessment of no/some/severe pallor as predictor of anaemia in health surveys at community level and in clinical practice in an out patient department (OPD) and in a hospital ward in rural Tanzania. METHODS: The study was undertaken among 6-36 months old children. Pallor was evaluated as a combined assessment of conjunctiva, tongue and palms and categorised as no, some or severe pallor. Packed cell volume (PCV) was measured and related to pallor. FINDINGS: A total of 740 examinations were performed at village, OPD and in the hospital ward. The prevalences of severe pallor were 0%, 1.5% and 7% respectively. The prevalences of any pallor were 14%, 41% and 86%. The prevalences of severe anaemia (PCV<21%) were 1%, 5% and 81% and of any anaemia (PCV<33%) 68%, 73% and 98%. Severe pallor could not detect severe anaemia. The sensitivities were only 0%, 0% and 8%. The sensitivities of any pallor to detect severe anaemia were however 86% and 98% for children at the health care facility level, but still of relatively poor predictive values since the specificities were only 61% and 68%. INTERPRETATION: Division of pallor into some or severe degrees was of no use at any health care level. The identification of any pallor was of no use at village level, but it may possibly be of some value as a screening test for severe anaemia at health care facilities, if additional assessment is included in view of the low specificity and positive predictive value of the finding.

Anemia↗

The association of pallor with haemoglobin concentration and mortality in severe malaria.

To identify a marker associated with poor outcome in severe malaria that requires no technology, the relationship between the presence of pallor and mortality was reviewed retrospectively in 291 Zambian children with cerebral malaria. The mean (S.D.) haemoglobin concentration among the 222 children assessed as having pallor on admission was significantly lower than that among the 69 children not considered to have pallor [6.0 (1.9) v. 9.2 (1.6) g/dl; P < 0.0005]. Thirty-nine (17.6%) of the children presenting with pallor died, compared with only five (7.2%) of those without pallor (P = 0.036). The adjusted odds of death in children with pallor on admission was 2.8 times higher than that in children without pallor (95% confidence interval = 1.03-7.7; P = 0.044). The clinical observation of pallor may therefore identify children with low haemoglobin concentrations and a high risk of mortality. Whether mothers and village health workers can be taught to recognize pallor in a child with malaria and then to seek early medical attention will need to be determined in further studies.

Antimalarials↗

Digital image analysis of optic nerve head pallor as a diagnostic test for early glaucoma.

We developed a computer-based technique to quantify optic nerve head pallor from videographically acquired digitized optic nerve images and tested the ability of pallor measurements to discriminate between normal eyes and eyes with early glaucoma. Corresponding pixel values from images obtained under 540 nm (green) and 640 nm (red) light with a videographic fundus camera were used to quantify optic nerve head pallor. A pallor density histogram was calculated for each eye, and contained values between 0 (red) to 1 (white). A measure of the distribution width of the histogram provided pallor measurements standardized to the measurements of the large veins of the disc. A database of one eye each of 44 normal controls and 70 patients with early open angle glaucoma was used to test the measurements for diagnostic sensitivity and specificity. These standardized pallor measurements did not perform better than absolute pallor measurements to discriminate between normal and glaucomatous eyes. The sensitivity and specificity of standardized pallor measurements (49% and 57%, respectively, for this database) were not as good as those for stereoscopic measurements of disc rim area in the same database (70% and 73%). Pallor measurements of this type do not appear to be sensitive or specific indicators of early glaucoma.

Aged↗

Videographic quantification of optic disc pallor.

Digitized images of the optic disc, acquired videographically (Rodenstock Analyzer) under green (540 nm) and red (640 nm) illumination, were used to quantify optic disc pallor. The pallor density of each pixel was defined as twice the reflectance under green illumination divided by the sum of the reflectance under red and green illumination. Pallor densities can range from 0 (red) to 1 (white); typical median values were 0.25 for vessels, 0.40 for healthy disc rim, and 0.70 for the lamina cribrosa. The variability of pallor measurements using this technique was determined. Two uniform color fields (Farnsworth-Munsell 100-Hue Test color chips 1 and 18) were imaged five times each using a model eye. Significant (P less than 0.0001) drift of mean pallor densities occurred between images of both sets. The optic discs of seven normal eyes and of seven glaucomatous eyes were imaged nine times each. The non-normal frequency distribution of pallor densities for each image was described by trimmed means and a measure of distribution width. Variability was defined as the standard deviation of the measurements divided by the full scale pallor density. The variability of the trimmed means increased with pallor density (r = 0.99, P less than 0.0001). The variability of distribution width was smaller than that of the mean values, and averaged 3.4% in normal and glaucomatous eyes. Videographic reflectometry may provide useful, quantitative measurements of optic disc pallor.

Glaucoma↗

The relation of conjunctival pallor to the presence of anemia.

OBJECTIVE: To determine the value of conjunctival pallor in ruling in or ruling out the presence of severe anemia (hemoglobin < or = 90 g/L) and to determine the interobserver agreement in assessing this sign. DESIGN: Patients were prospectively assessed for pallor by at least one of three observers. All observations were made without information of the patient's hemoglobin value or of another observer's assessment. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENTS: Three hundred and two medical and surgical inpatients. MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) calculated for conjunctival pallor present, borderline, and absent were as follows: pallor present, LR 4.49 (95% confidence interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers were 0.75 and 0.54. CONCLUSIONS: The presence of conjunctival pallor, without other information suggesting anemia, is reason enough to perform a hemoglobin determination. The absence of conjunctival pallor is not likely to be of use in ruling out severe anemia. With well-defined criteria, interobserver agreement is good to very good.

Adult↗

The utility of pallor detecting anemia in under five years old children.

The diagnosis and management of anemia, which affects a significant proportion of young children in developing countries, largely depends on the clinical assessment for pallor. This study was conducted with the aim of evaluating the utility of pallor in detecting anemia. Children aged 2 to 60 months who visited the pediatric outpatient department of Jimma Hospital over 3 months period were assessed for the presence and degree of pallor in 4 anatomic sites (conjunctivae, tongue and buccal mucosa, nailbeds, palm) by trained nurses. Hemoglobin was then determined using the HemoCue method. Individuals involved in clinical examination did not have access to the laboratory results before documenting their findings. The mean hemoglobin in the 574 children examined was 11.03 gm/dl, and about 46% had anemia. Children younger than 2 years were found to have a higher prevalence of anemia as compared to older children (p < 0.001). Palmar pallor, with a sensitivity of 58%, had the highest sensitivity to detect moderate anemia as compared to other anatomic sites. The presence of either palmar or conjunctival pallor increased the sensitivity to 73%. The inter-observer agreement was highest for conjunctival pallor (kappa value = 0.81). The findings of the study suggest that pallor of a single anatomic site does not have adequate sensitivity to detect moderate anemia. We recommend further studies to look at the performance of severe pallor in correctly identifying severe anemia. Furthermore, the magnitude and causes of anemia need to be studied in a community setting.

Age Factors↗

Pallor as a clinical sign of severe anaemia in children: an investigation in the Gambia.

Anaemia associated with malaria is a major public health problem in African countries. Since most primary health facilities have to rely on physical signs and not laboratory tests to detect anaemic patients who need referral for blood transfusion, we have assessed the reliability of simple clinical signs to predict severe anaemia. A trained field assistant examined 368 children admitted to a tertiary care hospital, assessing the pallor of their eyelids (conjunctiva), palms and nailbeds, counting the respiratory rate, and looking for signs of respiratory distress. After the children's admission, their packed cell volume (PCV) was measured, and the need for transfusion and the outcomes were noted. A second observer examined 173 of these children so that interobserver variability in the detection of clinical signs could be assessed. A total of 27% of the 368 children had a PCV of < 15%. In a multiple regression analysis, definite pallor of the conjunctiva, definite pallor of the palms, and a "sick" appearance of the child were identified as independent significant predictors of a PCV of < 15%. The best predictor was a combination of definite pallor of the conjunctiva and pallor of the palms, with a sensitivity of 80% and a specificity of 85%. Inclusion of signs of respiratory distress did not improve the prediction. Pallor was a reproducible sign (weighted kappa statistic for the comparison between two observers: kappa = 0.6 for conjunctival pallor). We conclude that pallor can be used as a sign for referring children who may require blood transfusion.

Anemia↗

Three-dimensional evaluation of optic disc pallor in open angle glaucoma.

We evaluated the extent of pallor on the walls of the optic cup three-dimensionally using simultaneous stereophotographs of the optic discs of 29 normals, 29 ocular hypertensives and 28 primary open angle glaucomas. Pallor was located at the bottom of the optic cup. Pallor ascends the walls of the cup as its extent increases. Statistically significant differences in the extent of pallor in all four quadrants of the optic cup were observed, with the glaucomas having greater extents of pallor than ocular hypertensives, and the ocular hypertensives greater than the normals. The greatest percentage increase in mean pallor from normals to open angle glaucomas occurred on the nasal and inferior walls. This differential extent of pallor could be useful in characterizing ocular hypertension and chronic open angle glaucoma.

Adult↗

Evaluation of clinical pallor in the identification and treatment of children with moderate and severe anaemia.

BACKGROUND: Anaemia from malaria is a common problem in developing countries. Blood transfusion in developing countries is available in few hospitals. Children who are severely anaemic and may require urgent blood transfusion usually present to peripheral first-level health facilities from where they must be referred to hospitals. Since most peripheral facilities do not determine haemoglobin levels, the decision on referral has to be made on clinical grounds. OBJECTIVES: To evaluate the sensitivity and specificity of clinical pallor of the palms, nailbeds, conjunctivae, buccal mucosa or tongue against haemoglobin values and their reproducibility among health workers. METHODS: A total of 2540 children 2 months to 5 years of age presenting to a rural health centre in Ethiopia were enrolled. Clinically detected pallor was compared with measured blood haemoglobin concentrations. RESULTS: Any anaemia (haemoglobin < 11 g/dl) was found in 61% of the children. Severe anaemia (haemoglobin < 5 g/dl) was found in 4%. The presence of any pallor clinically correlated with moderate anaemia (haemoglobin level < 8 g/dl) could be detected with a sensitivity of 95% and a specificity of 64-68% when the palm and nailbeds were used and a sensitivity of 84% and a specificity of 81% when the conjunctivae were used. Severe anaemia was detected clinically as severe pallor in 50-56% of cases (with a specificity of 95-96%). Agreement between physicians was highest for conjunctivae and nailbed pallor (87%) and lowest for palm pallor (73%). Using multivariate analysis, identification of a systolic ejection murmur or altered sensorium, the presence of splenomegaly or malarial parasitaemia were independently predictive of severe and moderately severe anaemia. CONCLUSIONS: Moderate and severe anaemia can be identified clinically in most cases for treatment and referral purposes. A systolic ejection murmur, altered sensorium, the presence of splenomegaly or malarial parasitaemia may be used as additional tools in considering urgent referral for blood transfusion.

Anemia, Iron-Deficiency↗

Recognition of pallor associated with severe anaemia by primary caregivers in western Kenya.

OBJECTIVES: To explore which pallor signs and symptoms of severe anaemia could be recognized by primary caregivers following minimal instructions. METHODS: Data from three community-based cross-sectional surveys were used. Test characteristics to predict haemoglobin (Hb) concentrations < 5 and < 7 g/dl were compared for different combinations of pallor signs (eyelid, tongue, palmar and nailbed) and symptoms. RESULTS: Pallor signs and haemoglobin levels were available for 3782 children under 5 years of age from 2609 households. Comparisons of the sensitivity and specificity at a range of haemoglobin cut-offs showed that Hb < 5 g/dl was associated with the greatest combined sensitivity and specificity for pallor at any anatomical site (sensitivity = 75.6%, specificity = 63.0%, Youden index = 38.6). Higher or lower haemoglobin cut-offs resulted in more children being misclassified. Similar results were obtained for all individual pallor sites. Combining a history of soil eating with pallor at any site improved the sensitivity (87.8%) to detect Hb < 5 g/dl with a smaller reduction in specificity (53.3%; Youden index 41.1). Other combinations including respiratory signs or poor feeding resulted in lower accuracy. CONCLUSION: Primary caregivers can recognize severe anaemia (Hb < 5 g/dl) in their children, but only with moderate accuracy. Soil eating should be considered as an additional indicator of severe anaemia. The effect of training caretakers to improve recognition of severe anaemia and care-seeking behaviour at the household level should be assessed in prospective community-based studies.

Anemia↗

Clinical pallor is useful to detect severe anemia in populations where anemia is prevalent and severe.

Clinical pallor is recommended as a simple way to detect severe anemia, but more data are needed on its accuracy and usefulness when assessed by nonphysicians in diverse settings. We measured hemoglobin and trained non-physician health workers to assess clinical pallor of the conjunctiva, palm and nail beds in five population samples in Nepal and Zanzibar, where severe anemia is common. In total, 5,760 individuals were examined, 3,072 of whom were anemic and 192 of whom had severe anemia (hemoglobin <70 g/L). The prevalence of pallor did not correspond to the prevalence of anemia or severe anemia in the groups studied. However, in all studies, pallor at each anatomical site was associated with a significantly lower hemoglobin concentration. The relative performance of different anatomical sites was not consistent among studies, and we recommend that multiple sites be assessed. Pallor at any of the three sites detected severe anemia with >84% specificity. However, the sensitivity varied from 81% in Nepalese postpartum women to 29% in Zanzibari preschoolers in 1996. Overall estimates for sensitivity and specificity were 50 and 92%, respectively. Although imperfect, use of pallor to screen and treat severe anemia by primary care providers is feasible and worthwhile where severe anemia is common. Usually, the majority of persons with severe anemia will be detected at practically no cost. Many people who are not severely anemic will also receive treatment, but the costs of this error are low compared to the benefits.

Adolescent↗

Computerized measurement of the three-dimensional distribution of optic disc pallor.

PURPOSE: To describe a method which provides quantitative measurements of the surface area of pallor in each quadrant of the three-dimensional optic cup, using photogrammetric measurements from simultaneous stereophotographs and computerized image analysis. METHODS: Simultaneous stereophotographs of one normal subject and two subjects with primary open angle glaucoma were digitized and analyzed for depth measurements. The boundaries of the optic disc, optic cup and region of pallor were identified. Pallor/disc and pallor/cup ratios were subsequently calculated for the superior, temporal, inferior and nasal walls. RESULTS: A digitized photograph and a Laplacian-filtered image were obtained for each eye to be studied. After processing each stereo pair through a similarity sequential detection-based algorithm, depth measurements are represented as a grey scale image, a contour plot, and a wire mesh, with the boundaries of the optic disc, optic cup and pallor superimposed. Ratios are given of the surface area of pallor to the surface area of the disc and the surface area of pallor to the surface area of the cup, by quadrant. CONCLUSIONS: Determination of surface area of pallor to cup may be useful in detecting early visual field loss in glaucoma and neurological disease.

Adult↗

Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis.

BACKGROUND: Anaemia is highly prevalent in children of developing countries. It is associated with impaired physical growth and mental development. Palmar pallor is recommended at primary level for diagnosing it, on the basis of few studies. The objective of the study was to systematically assess the accuracy of clinical signs in the diagnosis of anaemia in children. METHODS: A systematic review on the accuracy of clinical signs of anaemia in children. We performed an Internet search in various databases and an additional reference tracking. Studies had to be on performance of clinical signs in the diagnosis of anaemia, using haemoglobin as the gold standard. We calculated pooled diagnostic likelihood ratios (LR's) and odds ratios (DOR's) for each clinical sign at different haemoglobin thresholds. RESULTS: Eleven articles met the inclusion criteria. Most studies were performed in Africa, in children underfive. Chi-square test for proportions and Cochran Q for DOR's and for LR's showed heterogeneity. Type of observer and haemoglobin technique influenced the results. Pooling was done using the random effects model. Pooled DOR at haemoglobin <11 g/dL was 4.3 (95% CI 2.6-7.2) for palmar pallor, 3.7 (2.3-5.9) for conjunctival pallor, and 3.4 (1.8-6.3) for nailbed pallor. DOR's and LR's were slightly better for nailbed pallor at all other haemoglobin thresholds. The accuracy did not vary substantially after excluding outliers. CONCLUSION: This meta-analysis did not document a highly accurate clinical sign of anaemia. In view of poor performance of clinical signs, universal iron supplementation may be an adequate control strategy in high prevalence areas. Further well-designed studies are needed in settings other than Africa. They should assess inter-observer variation, performance of combined clinical signs, phenotypic differences, and different degrees of anaemia.

Africa↗

Quantitative evaluation of optic disc pallor in pseudotumor cerebri patients.

We quantified optic disc pallor in patients with pseudotumor cerebri with the Rodenstock Optic Nerve Head Analyzer before and after optic nerve sheath decompression. Mean frequency distribution of pallor peaked between the pallor values of 0.10 and 0.20 in four pseudotumor cerebri patients and between 0.50 and 0.60 in five normal subjects. The red dominant pallor reflectance in pseudotumor cerebri patients decreased significantly and shifted toward the reflectance of normal subjects gradually during the 9 weeks after successful optic nerve sheath decompression, coinciding with the ophthalmoscopic resolution of papilledema. The computerized pallor measurement with the Rodenstock Optic Nerve Head Analyzer allows an objective and quantitative assessment of papilledema in pseudotumor cerebri patients.

Adult↗

Morphological studies on cerebral cortical lesions induced by transient ischemia in Mongolian gerbil--diffuse and peripheral pallor of the neuronal perikarya.

Unilateral transient cerebral ischemia was produced in Mongolian gerbils by clipping the left common carotid artery for 1 h. About 60% of the gerbils with neurological symptoms had post-ischemic seizures. The majority of those that had seizures died within a few days, and sections of their cerebral cortices contained many dark and shrunken neurons. However, the gerbils that did not have seizures survived without any severe complications. In the cerebral cortex of the latter, the neurons with diffuse or peripheral pallor of the perikarya were seen along with a small number of dark and shrunken neurons. Diffuse pallor occurred within a few hours following ischemia in layers III, V, and VI, and disappeared 1 or 2 days after recirculation. Electron microscopically, these neurons showed dispersion of ribosomes, simple and elongated profiles of rough endoplasmic reticulum (r-ER), clustered vacuoles, and mild to moderate mitochondrial swelling. Occasional net-like tubulomembranous structures, probably derived from r-ER, were observed. On the other hand, peripheral pallor became apparent after 5 days following ischemia, usually involving layer II first and gradually extending to the deeper layers. Concomitantly, the amount of neuropil decreased and the dendrites exhibited tortuosity and irregularity in layer II. Electron microscopically, these neurons showed marked swelling of peripheral perikarya and polyribosomes and organelles were located peripherally to the nuclei. In addition, numerous degenerated axon terminals and distended dendrites were observed around the neurons. These observations indicate that diffuse pallor represents damage directly induced by ischemia and subsequent recirculation, while peripheral pallor is the delayed and remote effect of ischemia, probably due to degeneration of neuronal processes.

Animals↗

Neuroretinal rim area measurements by configuration and by pallor in ocular hypertension and glaucoma.

PURPOSE: The purpose of this study is to examine the differences between measurements of neuroretinal rim area of the optic disc defined by configuration and by pallor. METHODS: One hundred seventy-one patients were studied (59 with glaucoma, 96 ocular hypertensive patients, and 16 controls). The magnification-corrected neuroretinal rim area was measured from black-and-white stereoscopic paper prints. The central area of pallor was measured using computer-assisted image analysis techniques. The percentage of central area of pallor was converted into mm2, and an estimate of neuroretinal rim area defined by color was calculated. RESULTS: The correlation between the measurements of neuroretinal rim area by configuration and by pallor was statistically highly significant (r = 0.89, P less than 0.0001). No consistent differences between measurements were found in different diagnostic groups, or in different stages or types of glaucomatous optic disc abnormality. The correlation of changes of both measurements during a 9-year follow-up period also was statistically significant (r = 0.68, P less than 0.001). CONCLUSION: In clinical routine measurements of the neuroretinal rim area, using both configuration and pallor definition does not seem to add to the information.

Adult↗

Decrease of optic disc cupping and pallor of ocular hypertensives with timolol therapy.

PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on optic disc cupping and pallor in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to placebo or 0.5% timolol drops to both eyes in a double masked clinical trial. Measurements of ocular pressure and photographs of the optic disc for cupping by photogrammetry and pallor by computerized image analysis were made at about 3 month intervals, for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol developed a significant decrease in ocular pressure and a significant decrease in optic disc cupping with a smaller decrease in pallor compared to subject treated with placebo. Multivariate analyses indicated that the decrease of optic disc cupping and pallor was not associated with the ocular pressure on treatment or the decrease in ocular pressure during the trial. CONCLUSION: Timolol treatment was associated with a decrease in optic disc cupping and pallor. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.

Double-Blind Method↗