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Purpose: To identify and quantify the role of capillary leakage of the optic nerve head in digital fluorescein angiography in normal subjects and patients with open-angle glaucoma., Methods: We conducted a prospective cross-sectional study in the Department of Ophthalmology of the Technical University of Aachen. Thirty patients with primary open-angle glaucoma (POAG) and 30 healthy age-matched subjects were included. Fluorescein angiograms were performed using the scanning laser ophthalmoscope. The fluorescence of the optic nerve head and the surrounding retina (ratio of leakage) was measured using digital imaging analysis in the late phases of the angiogram (9-10 min)., Results: The ratio of optic nerve head fluorescence to retinal reference loci was significantly increased (p=0.01) in patients with glaucoma (POAG, 1.38+/-0.34) compared with normal subjects (1.20+/-0.19). Intraocular pressure (p=0.0001), visual field indices (mean deviation, p<0.0001; pattern standard deviation, p<0.0001; corrected pattern standard deviation, p<0.0001), and cup to disc ratios (p=0.02) differed significantly between the groups. Age and systolic and diastolic blood pressure showed no significant differences between groups., Conclusion: Fluorescein angiography revealed significantly increased vascular leakage of glaucomatous optic nerve heads. An endothelial disruption and fluorescein leakage might be the result of mechanical stress at the level of the lamina cribrosa and/or a sign of ischemic damage. This measurement approach might enable us to judge the severity of optic nerve head leakage, and it is a potential way to evaluate therapeutic regimens.

Purpose: The purpose of this study was to determine the distribution of retinal nerve fiber layer thickness by quadrant in healthy eyes., Patients and Methods: Forty subjects with healthy eyes were included in the study. A complete ophthalmic examination was performed, including determination of visual fields by automated perimetry. The subjects had no family history of retinal disease or glaucoma. Forty right eyes and 40 left eyes were measured. Retinal nerve fiber layer thickness was measured using simultaneous stereophotographs with stereophotogrammetry at the disc margin. For the total disc and four quadrants, absolute retinal nerve fiber layer thickness and optic disc area was determined using a magnification correction formula., Results: Comparison of the quadrants showed that the retinal nerve fiber layer thicknesses of the superior, inferior, and nasal quadrants were significantly thicker than the temporal quadrant (P = 0.00006 for right and left eyes). No significant differences were observed between the superior, inferior, and nasal quadrants in the right eye. In the left eye, the superior retinal nerve fiber layer thickness was significantly greater than the inferior (P = 0.028) and nasal retinal nerve fiber layer thicknesses (P = 0.00006), while the inferior was not significantly different from the nasal. No significant difference in quadrant retinal nerve fiber layer thickness was noted between eyes., Conclusions: Measurements of retinal nerve fiber layer thickness in healthy eyes show the thinnest quadrant to be the temporal, with the other three quadrants having similar thicknesses. This pattern corresponds to the histologic measurements of retinal nerve fiber layer thickness.

Purpose: To determine regional differences in the circulation of the optic disc, the peripapillary choroid and the retinal vessels using the techniques of computerized image analysis and fluorescein angiography., Methods: Ten young normal subjects were studied. Fluorescein angiography was performed with a scanning laser ophthalmoscope. The rate of filling of fluorescein or slope was measured in the four quadrants of the optic disc, the peripapillary choroid and the major retinal arteries and veins. A total of 125 points was measured from each image of the fluorescein angiograms for a total of 20 to 30 images. Retinal vessel width was measured using computerized image analysis., Results: Comparison of the rates of filling of fluorescein or slopes showed significant differences from zero among the four quadrants of the optic disc (p= 0.01 to <0.02), of the peripapillary choroid (p=0.01 to <0.05) and among the major retinal arteries (p=0.01 to <0.02) and retinal veins (p=0.02 to <0.05). No significant differences were noted between the quadrants for retinal arterial width with the retinal veins only showing a significant difference between the inferior nasal and inferior temporal vein (p=0.02 to <0.05)., Conclusion: Evaluation of the circulation of the optic disc, retina, and peripapillary choroid should take into account regional differences among these structures.

Purpose: To determine if there were significant differences between the number of red blood cell ouabain binding sites in normals and untreated ocular hypertensives plus one open-angle glaucoma patient., Methods: We measured the binding of (3)H ouabain to erythrocyte membranes of 23 normals, 25 ocular hypertensives and one open-angle glaucoma. We also measured the levels of plasma cortisol and digoxin in these subjects. Characteristics of cupping of the optic disc and thickness of the retinal nerve fiber layer, as well as area of optic disc pallor of these subjects were measured by stereophotogrammetry and by computerized image analysis from single and stereo photographs., Results: The number of (3)H ouabain binding sites was observed to be significantly less in the ocular hypertensives and one glaucoma compared to the normals (p = 0.0009). In multi-variate analyses, to determine what other factors affected this difference, there was a significant negative association with mean intraocular pressure (p = 0.003) (average of both eyes) and total cup volume (average of both eyes) (p = 0.005), diagnosis of ocular hypertension and glaucoma (p = 0.0005) and male gender (p = 0.019). There was a significant positive association with plasma cortisol levels (p = 0.048), and diastolic blood pressure (p = 0.037)., Conclusions: The number of (3)H ouabain binding sites in red blood cells decreases significantly with increasing ocular pressure and increasing cup volume indicating the possible presence of an increased systemic endogenous digoxin-like inhibitor and/or difference in the isozymes of Na(+), K(+)-ATPase which may be associated with increased levels of plasma cortisol in ocular hypertensives and glaucomas.

Computerized image analysis, including fluorescein angiography, was used to evaluate the retinal, choroidal and optic disk blood flow in 16 patients with normal-tension glaucoma (NTG) and to correlate this measurement with visual fields, retinal vessel width, optic disk pallor and blood pressure (BP). The angle of the ascending slope of the fluorescein dye curve was measured as an index of blood flow from the densitometric and time curves of the fluorescein angiograms in the optic disk, peripapillary choroid, retinal artery and vein for each quadrant. While the ascending slope as well as the retinal vessel width were most reduced in the inferior and nasal regions, the mean threshold was lowest in the superior and nasal quadrants. There were positive significant correlations between artery width and threshold value, between angles of slopes and pallor. In addition, systolic BP had a negative correlation with pallor, and diastolic BP had a positive one with slope in the choroid. These results indicated the probable association of a decrease in retinal, choroidal and optic disk blood flow in the inferior and nasal quadrants as well as vessel width in the inferior nasal quadrant with visual field loss in the superior quadrant, and also demonstrated an increasing blood flow for enlargement of pallor. A decrease in BP was found to be related to reduced blood flow in choroid and optic disk impairment., (Copyright 2000 S. Karger AG, Basel)

Purpose: This randomized, double-masked, placebo-controlled, two-period crossover study was conducted to investigate the effects of 0.5% timolol maleate in gel-forming solution on intraocular pressure (IOP) and blood circulation in the optic nerve head in patients with untreated ocular hypertension., Methods: The effects of 0.5% timolol in gel-forming solution on IOP and optic nerve head capillary blood speed were studied in 12 patients with untreated ocular hypertension. Optic nerve capillary blood speed was measured using the laser Doppler technique before and at the end of each treatment period., Results: In each patient, IOP decreased after treatment with timolol (mean decrease 16.8% versus placebo). Systemic blood pressure and pulse rate did not differ significantly after treatment with topical timolol from values after placebo. The mean change from baseline in Doppler broadening was 10.6% greater after treatment with timolol than after placebo. There was no significant change in mean Doppler broadening from baseline after treatment with either timolol or placebo. However, optic nerve head capillary blood speed increased in six patients, and was within the range of placebo response in six patients after treatment with timolol. Spearman correlation analysis of the baseline with Doppler broadening measurements after treatment showed a correlation for placebo but not for timolol. The percent change in Doppler broadening after timolol treatment was correlated with iris color., Conclusion: These results indicate that administration of timolol for 4 weeks reduces IOP in patients with ocular hypertension and generally does not change the blood circulation in the optic nerve head. Individual patients, however, showed variable changes in optic nerve head circulation after topical administration of timolol. Although the sample size was small, these changes in optic nerve head circulation were correlated with iris color.

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.

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.

Studies using fluorescein angiography have shown that two types of circulatory defects occur in the optic disk and retina of open-angle glaucomatous eyes. The first is a defect of the microcirculation of the optic disk characterized as a fluorescein defect. Such defects begin as small areas of relatively little filling of the small vessels of the disk with fluorescein. The areas of defect show leakage for both fluorescein and indocyanine green. These defects increase in size and number with the progression of the disease. Fluorescein defects are significantly correlated with visual field loss and retinal nerve fiber layer loss. The second circulatory defect is a decrease of flow of fluorescein in the retinal vessels, especially the retinal veins, so that the greater the age, diastolic blood pressure, ocular pressure and visual field loss, the less the flow. Both the optic disk and retinal circulation defects occur in untreated ocular hypertensive eyes. These observations indicate that circulatory defects in the optic disk and retina occur in ocular hypertension and open-angle glaucoma and increase with the progression of the disease.

We matched by disk area size 23 eyes of patients with glaucoma-like disks (physiological cups) with normal ocular pressures and no visual field loss with 23 eyes of normal subjects. Using stereophotogrammetry we found a significant decrease in retinal nerve fiber layer thickness in the eyes with glaucoma-like disks compared to the normal eyes (P = 0.0081), especially in the nasal quadrant (18.1%). A similar significant decrease was noted in the neuroretinal rim area and a significant increase in cup volume, area, depth and slope for the total disk and its quadrants. The use of computerized image analysis also showed a significant increase in pallor area for glaucoma-like disks compared to normal disks. Eyes with glaucoma-like disks or physiological cups showed evidence of an optic neuropathy and may be manifesting the same damage to the optic nerve occurring in high pressure 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.

Laser scanning tomography (LST) and computed stereophotogrammetry (CSP) are sophisticated diagnostic tools for the three-dimensional analysis of optic nerve head topography. The two methods are based on different physical principles. To compare the information about the shape of the cup of an optic nerve head obtained by LST and CSP, we evaluated the volume profile (VP; i.e., the cross-sectional area of the cup from top to bottom) in 36 discs of 36 patients (20 control group discs C, 16 glaucoma discs G). The Spearman correlation coefficient between the photogrammetric and the laser scanning VP-slope measurements was rs = 0.931; P < 0.001 (rs = 0.935 G, P < 0.001; rs = 0.910 C, P < 0.001). The results suggest that confocal laser scanning provides readings of the shape of the optic disc cup that are similar to the measurements of computed stereophotogrammetry.

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.

A group of 110 eyes with untreated ocular hypertension, 94 being non-exfoliative and 16 exfoliative and in addition 10 glaucomatous eyes were selected for this study. The optic nerve head was examined by ophthalmoscopy and a drawing was made of the estimated cupping. The disc pallor was measured from disc photographs in a double masked manner at the same time. The possibility to detect early glaucomatous damage by a single examination will be discussed and the two methods will be compared. This study indicates that an increasing vertical diameter of disc pallor might have a predictive value.

The authors determined asymmetrical differences in optic disc cupping and pallor between the right and left eyes of 57 control subjects and 75 patients with ocular hypertension. Photogrammetry was used to measure the optic disc cup, and computerized image analysis was used to measure the optic disc pallor for the total disc and its quadrants. Generally, for control and ocular hypertensive eyes, the median values of cupping and pallor were significantly larger in the left eye than in the right, except for depth in the inferior quadrant (right eye minus left eye = 9.3%, P = 0.000) and pallor in the nasal quadrant (right eye minus left eye = 21.3%, P = 0.01), which were preferentially larger in the right eye than in the left in ocular hypertensive eyes. Ocular hypertensive eyes also showed a greater difference between the right and left eyes compared with control eyes for inferior depth (P = 0.06) and nasal pallor (P = 0.02). Detection of optic disc differences as a sign of ocular hypertension between the right eye and the left should evaluate the inferior and nasal quadrants of the disc.

We compared (1) the differences in the retinal nerve fiber layer between 26 patients with Alzheimer's disease and 30 age- and race-matched normal controls with use of blue-light high-resolution photography, (2) the differences in disc pallor between 30 patients with Alzheimer's disease and 32 controls with use of a boundary-tracking program and fundus photographs, and (3) the topographic disc variables between 26 patients with Alzheimer's disease and 36 controls with use of an optic nerve head analyzer. A higher proportion of patients with Alzheimer's disease had detectable nerve fiber damage as seen by red-free photography compared with controls. Although the pallor area-to-disc area ratio was not significantly different between patients with Alzheimer's disease and controls, the patients with higher pallor area-to-disc area ratios had higher Alzheimer's Disease Assessment Scale (ADAS) scores and longer durations of disease. Patients had an increased cup-to-disc ratio and cup volume and decreased disc rim area compared with controls. These variables also correlated significantly with ADAS scores and the duration of disease. The correlation among the optic nerve head changes and the ADAS scores in patients with Alzheimer's disease suggests a potential role for optic nerve head analysis in monitoring the progression of Alzheimer's disease and in assessing the effectiveness of any treatments developed.

Four patients with glaucoma-like discs, normal visual fields, and normal ocular pressures (less than 21 mmHg), first detected by direct ophthalmoscopy, were followed without treatment. Increased ocular pressures (greater than or equal to 21 mmHg) subsequently developed in these patients at an average of 8.1 years after the recognition of their glaucoma-like discs. Before the increased ocular pressure developed, two patients showed retinal nerve fiber layer loss and one showed optic disc hemorrhages. There are two possible hypotheses to explain this sequence of events. The first is that the optic discs and nerve fiber layer defects were produced by abnormal diurnal levels of ocular pressures or levels of ocular pressure, although less than 21 mmHg, which may be abnormal for the optic disc. The second hypothesis is that there are two independent events, one producing abnormalities in the optic disc and nerve fiber layer and a second producing the increased ocular pressure.

The topography and extent of localized areas of hypofluorescence or absolute filling defects of the optic discs of glaucomatous patients correlated positively with the loss of visual field. Filling defects tended to cluster at the inferior and superior poles of the optic disc and were closer to the disc margin than to the center. The location of the defects corresponded with the expected site of visual field loss. There was a positive correlation between the percent area of the filling defects and the degree of visual field loss. These observations support the concept that fluorescein filling defects of the optic disc in glaucoma represent areas of ischemia that are highly correlated with loss of visual field.

Measurements were made of the percent areas of optic disc cupping and pallor in ocular hypertensive eyes and normal eyes. The ocular hypertensive eyes showed significant increases in pallor but not in cupping compared to normal eyes. There was also a significant positive correlation of cupping with age in normal eyes but not in ocular hypertensive eyes. Fluorescein angiography of the optic disc showed an increase in the number and area of filling defects in ocular hypertensive compared to normal eyes. There were significant positive correlations in ocular hypertensives between percent area of filling defects with both age and systolic blood pressure which were not present with normal eyes. The optic disc changes which occur in ocular hypertensive eyes are primarily characterized by an increase in pallor and an increase in both the number and area of fluorescein filling defects.

One hundred seventy-one optic disc fluorescein angiograms of glaucomatous, ocular hypertensive, and normal patients were studied for the occurrence of areas of hypofluorescence or absolute filling defects in the rim, wall, and floor of the optic cup using disc stereo photographs compared with the fluorescein angiogram. The frequencies of involvement of the rim, wall, and floor of the cup by filling defects were determined. The wall of the cup has a greater percentage of filling defects in subjects with glaucoma than in ocular hypertensive or in normal subjects. The floor of the cup has more filling defects in normal subjects than in those with glaucoma. The involvement of the wall of the cup increases with the degree of visual-field loss in glaucoma. We suggest that, in glaucoma, the effect of ocular pressure is greater on the wall of the cup than on the floor of the cup.

Measurements of the human ocular fundus in the three spatial dimensions have not been absolute because measuring techniques have used the optical system of the eye as part of the total ophthalmoscopic system. The ophthalmoscopic magnification due to the total dioptric power of an individual eye can vary substantially from that of the average eye. A new method has been developed to form interference fringes on the fundus so that the fringe spacing can be calculated within a small error by using measured values. The photographed fringes then act as a scale at the fundus with the fringe spacings serving as the graduations, thus allowing accurate absolute measurements of the fundus through the interfering ocular media.

In a prospective study of untreated ocular hypertension 117 eyes were non-exfoliative and 20 eyes exfoliative. The percentage of optic disc pallor was significantly larger in the exfoliative than in the non-exfoliative group, whereas no significant differences were found in IOP or in the visual field.

Fluorescein angiograms of the optic disc were studied in 23 normal and 29 ocular hypertensive eyes. Significant differences in the frequency distributions of areas of defects were obtained between normal and ocular hypertensive eyes. Increased areas of filling defects were noted in ocular hypertensive eyes as compared to normals. There were also significant correlations of the areas of filling defects with age and systolic blood pressure in the ocular hypertensive eyes that were not present in the normals. These observations support the concept that fluorescein angiography of the optic disc demonstrates localized areas of impaired circulation that increase with ocular pressure, age, and systolic blood pressure. This technique may be useful in separating normal from the ocular hypertensive patient who shows changes in the circulation of the optic disc with increased ocular pressure.

In 24 ocular hypertensive patients, two optic disc fluorescein angiograms were obtained a mean of 3.9 years apart. Using computerized image analysis, we measured the area of pallor and the fluorescein-filling defect area within the disc and the fluorescein circulation parameters representing the filling rates of optic disc, choroid, and retinal vessels. The results indicated that increase in pallor and fluorescein-filling defect areas, as well as a slowed filling rate of the retinal veins, correlated with glaucomatous progression.

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.

An improved technique for high-contast, high-resolution fluorescein angiography of the optic disc has been developed that almost eliminates pseudofluorescence. Fluorescein angiography of the optic disc was performed on normal, ocular hypertensive, and glaucomatous patients. Rapid-sequence angiograms in the early arterial phases have demonstrated localized areas of hypofluorescence or filling defects of the optic disc. Two types of fluorescein filling defects were observed-absolute and relative. The number of absolute filling defects, which increased with degree of visual field loss, was greater in glaucomatous than in ocular hypertensive or normal eyes. Similarly, ocular hypertensive eyes showed a larger number of discs with filling defects than normal eyes. It is postulated that relative defects progress to absolute filling defects, which may be an indication of impending loss of visual field.

A comparison of two or more disc fluorescein angiograms performed on separate occasions was done on 60 eyes of normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. Clinically stable patients did not show any change in their disc angiographic filling patterns. Eyes that developed new visual-field defects with increased disc cupping and pallor correspondingly showed new absolute filling defects or areas of hypofluorescence. In those with established field defects, however, further changes in the visual field occurred without obvious changes in the disc fluorescein filling defect. Surgical lowering of intraocular pressure with or without decrease in disc cupping and pallor did not result in visible improvement of the disc angiographic pattern. Thus, the development of new visual-field defects is associated with changes of the circulation of the optic disc.

Photographs of the optic discs and fluorescein angiograms of 31 patients with open-angle glaucoma and 43 patients with ocular hypertension were evaluated for nerve fiber layer (NFL) defects and absolute fluorescein filling defects. All of the glaucomatous eyes showed both defects. Of the 43 ocular hypertensive eyes, in which both NFL and absolute fluorescein filling defects were evaluated, 9% had only NFL defects, 19% had only fluorescein filling defects, 14% had both defects, and 58% had neither defect. The percent area of fluorescein defect in the optic disc increased with severity of NFL defect in glaucoma and ocular hypertension. This study confirms the relationship of fluorescein filling defects and NFL defects to glaucomatous abnormalities and thus the association between vascular damage to the optic nerve and axon loss in glaucoma. The earliest objective evidence of glaucomatous damage can be detected with a combination of NFL evaluation and optic disc fluorescein angiography.

Most ophthalmologists use subjective methods to evaluate the optic disc for abnormalities and changes that occur in ocular hypertension and glaucoma. We have developed new techniques that allow more accurate evaluation of the blood supply to the optic disc and of changes in disc cupping and pallor. To evaluate the blood supply we use the technique of fluorescein angiography of the optic disc. With this technique, we have found that fluorescein defects commonly appear in open-angle glaucoma and ocular hypertension and are more frequent and larger in glaucomatous and ocular hypertensive discs than in normal optic discs. Fluorescein angiography demonstrates distinct changes in the blood supply to the optic disc in the glaucomatous or ocular hypertensive eye. Cupping of the optic disc is measured by photogrammetry from stereophotographs, which provide three-dimensional measurements not only of the volume of the cup, but of the depth, the slopes of the walls of the optic cup, and the area of the surface opening. This technique also allows us to determine a volume profile of the cup: that is, its cross-sectional area from top to bottom. The volume profile characterizes the shape of the optic cup and shows distinct differences in shape between normal, ocular hypertensive and glaucomatous cups. Pallor is measured by computerized image analysis. This technique allows us to determine the percent area of pallor of the optic disc. These three techniques permit us not only to evaluate abnormalities, but to measure changes over time in the optic disc in ocular hypertension and glaucoma, thereby increasing our diagnostic capability and improving patient management.

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.

To detect early glaucoma-associated changes in the optic disc cup, the authors analyzed reproducibility of optic disc cup measurements by photogrammetry of three age-matched groups: 10 normal, 10 ocular hypertensive, and 10 glaucomatous subjects. For each eye, three simultaneous stereophotographs were taken on the same day and one measurement was made for each stereophotograph. In order to reduce the effects of refractive error of the eye and photographic magnification, the authors computed cup parameters as relative measurements, ie, a ratio to the optic disc area. The median coefficients of variation for glaucomatous eyes were 4.5% for cup volume/disc area, 6.1% for cup depth/disc area, and 4.7% for cup area/disc area. Coefficients of variation of normal and ocular hypertensive subjects were slightly larger than those of glaucomatous subjects. Coefficients of variation generally were larger for quadrants than for total disc area. These findings suggest that the photogrammetric technique is highly reproducible and sensitive and could be a valuable quantitative technique for the clinical study of glaucoma.

The authors have developed an objective, quantitative method for detecting optic disc cup changes that occur with time. Called stereochronometry, this new technique uses a stereoplotter to measure changes recorded in the combination of two single photographs taken of the same optic disc at different times. The reproducibility and sensitivity of stereochronometry were evaluated using a model eye. Stereochronometric measurements were significantly correlated with calibrated changes of depth and width of the cup of the model eye. Standard deviations for five measurements of cup changes without camera shift range from 2 microns to 18 microns, and errors (deviations of the mean of measurements from calibrated cup changes) ranged from -26 microns to +33 microns. Standard deviations and errors in the measurement of cup depth and width were significantly increased when the camera was shifted by 2.5 mm between photographs to simulate possible changes in photographic conditions.

Optic disc pallor was recorded in 53 eyes of 53 patients by means of global analysis with a video-ophthalmograph (Rodenstock Disk Analyzer) and computerized boundary analysis. The coefficients of correlation between the values obtained with the Rodenstock Disk Analyzer and those obtained with boundary analysis were r = 0.24 (p = 0.08) at the 0.29 cutoff level, r = 0.39 (p = 0.004) at the 0.39 level and r = 0.46 (p = 0.0005) at the 0.50 level. Although the correlation was significant, the correlation coefficients were not high. The Rodenstock Disk Analyzer uses global analysis, which does not take into account the spatial relationship of the pallor on the disc, whereas boundary analysis is sensitive to spatial relationship, which may account for the poor correlation.

We studied 48 patients who had glaucomalike disks with increased cupping and pallor, superior or inferior extension of cupping and pallor and asymmetry of cupping and pallor between eyes without increased intraocular pressure or visual field loss, and open angles. We compared these patients with a randomly selected group of 48 patients with primary open-angle glaucoma. The mean age of the patients with glaucomalike disks (45.1 +/- 16.1 years) was significantly younger than the group with open-angle glaucoma (63.8 +/- 11.3 years). Of the patients with glaucomalike disks, 11 (23%) had a family history of glaucoma, 75% of 22 eyes with optic disk fluorescein angiograms had abnormal readings, and 59% of 43 eyes with retinal nerve fiber layer defects had abnormal readings. Photogrammetric measurements of the left disk cups were compared in 22 of the patients with glaucomalike disks to 16 matched patients with primary open-angle glaucoma. The only statistically significant difference was that the patients in the glaucoma group showed a larger cup area (surface opening) of the inferior quadrant. Our findings suggest that some glaucomalike disks may be one variant of primary open-angle glaucoma.

A case of arteriosclerotic posterior ischemic optic neuropathy without optic disc edema is described and documented photographically. The development of optic disc cupping and pallor with ischemia in this patient supports the vascular basis for development of similar cupping and pallor in open angle glaucoma and low tension glaucoma.

The two-point fluorophotometry technique was used to analyze quantitatively absolute fluorescein filling defects or hypofluorescent areas in glaucomatous optic discs. Significant differences were found between hypofluorescent and normal fluorescent areas. The hypofluorescent areas had slower and lesser filling of fluorescein and a slower disappearance of fluorescein compared with normal fluorescent areas. Also, the hypofluorescent areas showed a slow and persistent accumulation of fluorescein. Age, blood pressure, ocular pressure, and percent area of optic disc pallor were significantly correlated with changes in the circulation in the areas of normal fluorescence and hypofluorescence. This study suggests a decreased blood flow and a smaller vascular bed together with narrower vessels and increased permeability of the vessels in the hypofluorescent areas.

Computerized image analysis was used to quantify objectively fluorescein angiograms of the optic disc, peripapillary choroid, and retina. Techniques were developed to measure fluorescein filling rates of the optic disc and the retinal vessels and the area of fluorescein filling defects within the optic disc. Two subjects, one with glaucoma and the other with ocular hypertension, showed increases of areas of fluorescein filling defects of the optic disc on follow-up and are presented here as examples of the application of these techniques. This methodology can be applied to the longitudinal follow-up of individual patients with glaucoma and retinal diseases, as well as to cross-sectional studies of patient populations.

Fluorescein angiography of the optic disc was performed on normal subjects, patients with nonmyopic open-angle glaucoma dna myopic open-angle glaucoma, normal myopes, patients with optic atrophy due to chiasmal pituitary tumors, and patients with sectorial ischemic optic neuropathy due to vascular hypotension. The normal myopes, those with optic atrophy secondary to pituitary tumor, and the ischemic optic neuropathy group had optic discs similar in appearance to those with open-angle glaucoma. Absolute fluorescein filling defects occurred only in patients with open-angle glaucoma and sectorial ischemic optic neuropathy. The filling defects in open-angle glaucoma appear to be specific, indicating that the blood supply to the anterior portion of the optic nerve is involved, as in ischemic optic neuropathy. Fluorescein angiography of the optic disc may be useful to differentiate open-angle glaucoma from other entities that have similar optic discs.

The optic discs of eight normal subjects were photographed on three separate visits under widely varying conditions. Each photograph was scanned by a television camera, converted to digital form, and then analyzed using computer image analysis techniques. The computer was programmed to delineate the boundary around the optic disc and the area of pallor. The percentage of disc pallor was then computed across the entire disc and for each disc quadrant. The reproducibility of the procedure was determined by evaluating several photographic parameters: camera flash intensity, film type, magnification, and centering of the disc in the photograph. The focus adjustment on the television scanner was also varied. Under carefully controlled conditions, results showed that the reproducibility of measuring the total percent of disc pallor was 2%. Results for reproducibility are also given for less than optimal conditions and for manual planimetry on the same set of photographs.

We evaluated whether the rate of occurrence of glaucomatous disk damage in eyes with an optic disk hemorrhage differed from the rate of occurrence in control eyes. We compared 24 patients with a disk hemorrhage to 24 control patients, who had been matched for diagnosis, disk appearance, and visual fields. Cup volume and cup-to-disk area ratio of the optic disk were measured using the stereophotogrammetric technique, and area of pallor was measured using computerized image analysis. We found that diabetes increased the probability that a patient would have a disk hemorrhage, and that a hemorrhage was associated with progression of glaucomatous disk changes in half of the cases during the mean 3.1-year follow-up period. However, the mean rate of glaucomatous disk damage in patients with a hemorrhage was not different from matched control patients. A disk hemorrhage is a sign of later disk damage, but it does not alter the rate of glaucomatous disk progression.

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.