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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

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

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

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

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

[High mean pallor value--a risk factor for deterioration of the visual field in glaucoma and ocular hypertension. A pilot study using the optic nerve head analyzer].

UNLABELLED: Does the disc parameter "mean pallor value" suggest a risk for further deterioration of visual field defects? PATIENTS: In 10 patients with ocular hypertension and 23 patients with primary open-angle glaucoma (Octopus 201, Humphrey perimeter) disc pallor was calculated by double examinations with the ONHA in 1987-1988, and a long-term follow-up of the visual field was performed. In all patients we also acquired information about the IOP level and visual field during the observation time from the ophthalmologists. Only one eye per patient was evaluated after randomized selection. RESULTS: In ocular hypertensive patients only 1 of 10 eyes showed deterioration of the visual field. In the glaucoma group 4 eyes out of 23 showed an increase in visual field loss. The eyes with a tendency to deteriorate had a higher mean pallor value compared with the mean value of the corresponding group [ocular hypertensives: 0.40 compared to 0.31 +/- 0.07 (0.02); POAG: 0.50 +/- 0.06 (0.03) compared to 0.33 +/- 0.08 (0.02); mean value +/- SE (SEM)]. The difference was statistically significant in the glaucoma group; Wilcoxon, Mann and Whitney U-test; P < 0.005. CONCLUSIONS: Taking into consideration all risk factors, the mean pallor value might help additionally to prognosticate the risk of deterioration of the visual field as far as 5-year follow-up allows this preliminary conclusion. The pallor value alone is not suitable for the follow-up of glaucoma patients because of the influence of increasing lens opacities and changes in the video system of the ONHA over years.

Follow-Up Studies

Scanning microdensitometry of optic disc pallor in glaucoma.

A scanning microdensitometric technique has been developed for measuring the optical density of black and white photographs of the optic disc. From the frequency distribution curve of all the densities of the whole area of the optic disc, a separate peak was identified as corresponding to the area of pallor of the optic disc. Areas of pallor were measured as percentage of areas of the total disc for normal, ocular hypertensive, open-angle glaucoma patients, and those with suspect discs. Median values of percent area of pallor showed correspondence with the clinical diagnosis, the glaucoma patients having significantly larger areas than the normal subjects. The microdensitometric technique provides an objective means of measuring the amount of optic dis pallor. It has potential usefulness for screening and for following up suspect and confirmed glaucomas to determine progression of the disease.

Densitometry

Reproducibility of pallor measurements with the optic nerve head analyzer.

One eye each of ten healthy volunteers was tested with the Rodenstock Optic Nerve Head Analyzer on ten separate occasions. A color-coded pallor map was developed for each examination. A color transparency of each pallor map was then obtained from the television monitor of the Optic Nerve Head Analyzer, using a camera mounted on a tripod at a fixed distance from the screen. A color-coded zone within the center of the disc was chosen for each set of ten studies, and the area of this zone was measured by boundary analysis with another computerized image analyzer, the Oasys Image Processor. There was wide intrasubject variation in all ten volunteers, suggesting that the pallor map generated by the Optic Nerve Head Analyzer, when used in the manner described in this paper, is not adequate for following subtle changes in optic nerve head pallor.

Humans

Measurements of reversibility of optic disc cupping and pallor in ocular hypertension and glaucoma.

Four cases are presented of young and elderly glaucoma patients who had both surgical and medical therapy and showed reversal of cupping and pallor of the optic disc. The cupping was measured by photogrammetry and the pallor by computerized image analysis from photographs of the optic disc. Two patients showed regression of visual field loss. The optic disc and visual field changes corresponded to the changes in ocular pressures, generally showing worsening with an increase in ocular pressure. With a decrease in ocular pressure there was regression of visual field loss and a decrease in cupping; pallor did not decrease consistently. The changes in cupping and pallor in some patients followed similar courses but in others behaved in an independent manner. It is proposed that these new sensitive and reproducible techniques for measuring changes in the optic disc may allow the detection of disc changes early in the disease, prior to visual field loss. If treatment is begun at this time, reversal of optic disc changes may occur.

Aged

Detection of increased pallor over time. Computerized image analysis in untreated ocular hypertension.

Computerized image analysis was used to measure changes in percent area of pallor of the optic disc in a retrospective study of a group of 16 normals and 39 untreated ocular hypertensives. The optic discs of the subjects were photographed on at least two visits at least one year apart (mean, 2 years). No significant changes in area of pallor for the normal group were observed between visits, except in the inferior quadrant of the left eye. The ocular hypertensive group showed a significant increase in area of pallor between visits for the total disc and for most quadrants of both eyes. Multiple regression analysis revealed that, in addition to ocular hypertension, the significant factors associated with a change in optic disc pallor were change of ocular pressure, standard deviation of the ocular pressures, presence of vascular hypertension, and standard deviation of vascular pulse pressures. Clinical implications of early detection of disc changes for follow-up and treatment of ocular hypertensives are discussed.

Adult

Evaluation of conjunctival pallor in the diagnosis of anaemia.

The diagnosis of anaemia using conjunctival pallor was evaluated using the concept of predictive values. The presence or absence of pallor in 951 individuals and their haemoglobin levels were matched, defining haemoglobin of 10 g dl-1 or less as representing anaemia. The sensitivity and specificity of the test of pallor were 18.6% and 95.8%, respectively. At 16.3% prevalence of anaemia the positive and negative predictive values were 46.3% and 85.8%, respectively. The findings suggest that conjunctival pallor as a screening test for anaemia may not be very reliable.

Adolescent