Studies on diameter distribution of axons in the optic pathway in human glaucoma

The distribution of diameters of axons and somas at the level of the optic nerve, lamina cribrosa and retina were compared between human glaucomatous eye and normal control eyes. At the level of lamina scleralis of the glaucomatous eye, there was a tendency for large nerve fibers to be lost in the arcuate nerve fiber area particularly in the inferior arcuate nerve fiber area, where the corresponding visual field defect was detected. The percentages of large axons and somas in the arcuate nerve fiber area decreased in the glaucomatous eye both at the level of the optic nerve, retina but most of all at the level of lamina cribrosa. These results suggest that the mode of optic nerve damage in early glaucoma is characterized by the selective damage of large nerve fibers, which is most severe at the lamina cribrosa.     

The contour of the juxtapapillary nerve fiber layer in glaucoma

Reliable structural markers for early glaucomatous optic nerve damage would facilitate the diagnosis of glaucoma at an early stage, possibly before visual field loss occurs. Computerized image analyses were used to develop and analyze new structural parameters for glaucomatous optic nerve damage. Multiple measurements of relative juxtapapillary nerve fiber layer height were made in glaucoma patients (n = 112), patients suspected of having glaucoma (n = 87), and in age-matched normal control subjects (n = 53). The average relative nerve fiber layer (NFL) height differed in glaucoma patients and normal subjects by 70 microns, but differences exceeded 100 microns at the superior and inferior poles of the disc. Mean values for "glaucoma suspects" were intermediate between those for the normal subjects and glaucoma groups. The ability of summary statistics of relative NFL height measurements to discriminate between normal and glaucomatous eyes was superior to that of the standard disc parameters cup-disc ratio, disc rim area, and cup volume. Measurements of relative NFL height correlated with indices of visual field loss; the strongest correlations occurred for measurements at the superior and inferior poles. Measurements of juxtapapillary NFL height may prove useful to detect glaucomatous optic nerve damage at an early stage and to accurately recognize progressive nerve damage over time.     

The optic nerve head in glaucoma: role of astrocytes in tissue remodeling

Primary open angle glaucoma is a common eye disease characterized by loss of the axons of the retinal ganglion cells leading to progressive loss of vision. The site of damage to the axons is at the level of the lamina cribrosa in the optic nerve head. The mechanism of axonal loss is unknown but elevated intraocular pressure and age are the most common factors associated with the disease. Previous studies in human glaucoma and in experimental glaucoma in monkeys have established a relationship between chronic elevation of intraocular pressure and remodeling of the optic nerve head tissues known clinically as cupping of the optic disc. This review focuses on the astrocytes, the major cell type in the optic nerve head. Astrocytes participate actively in the remodeling of neural tissues during development and in disease. In glaucomatous optic neuropathy, astrocytes play a major role in the remodeling of the extracellular matrix of the optic nerve head, synthesize growth factors and other cellular mediators that may affect directly, or indirectly, the axons of the retinal ganglion cells. Due to the architecture of the lamina cribrosa, formed by the cells and the fibroelastic extracellular matrix, astrocytes may respond to changes in intraocular pressure in glaucoma, leading to some of the detrimental events that underlie axonal loss and retinal ganglion cell degeneration.     

Correlation of structure and function in glaucoma. Quantitative measurements of disc and field

The relationship between quantitative structural measurements of the optic nerve head and quantitative measurements of the visual field in glaucoma was studied. Computerized videographic image analysis (Rodenstock Analyzer) was used to obtain cup-disc ratio, disc rim area, and cup volume in 50 glaucoma suspects and 37 glaucoma patients. The visual field indices, mean defect and loss standard deviation, were calculated from Octopus Program 32. There were statistically significant linear correlations between each of the optic nerve structural parameters and visual field mean defect and loss standard deviation. The strongest correlation was between disc rim area and visual field mean defect (r = -0.49), which are both global measures of glaucomatous damage. The correlations were not strong enough to readily allow the recognition of early nerve damage by the parameters analyzed thus far. Closer correlations may be evident if structural parameters can be found that more accurately reflect the number of surviving axons in the optic nerve head.     

Optic cup deepening spatially correlated with optic nerve damage in focal normal-pressure glaucoma.

PURPOSE: To evaluate whether deepening of the optic cup in patients with focal normal-pressure glaucoma is correlated with the location of most marked loss of neuroretinal rim and visual field. METHODS: Using morphometric evaluation of color stereo optic disc photographs of 102 eyes of 65 patients with focal normal-pressure glaucoma, the superior half of the optic disc was compared with the inferior half. RESULTS: In eyes in which the optic cup was deepest in the inferior half of the disc, the most pronounced rim loss was located inferiorly significantly more often than superiorly, and the most marked visual field loss was located superiorly significantly more often than inferiorly. In eyes in which the optic cup was deepest in the superior half of the disc, the most pronounced rim loss was located superiorly significantly more often than inferiorly, and the most marked visual field loss was located inferiorly significantly more often than superiorly. Correspondingly, in eyes in which the most marked rim loss was located inferiorly, the deepest optic cup part was located inferiorly significantly more often than superiorly, and vice versa. CONCLUSION: In focal normal-pressure glaucoma, location of the most marked deepening of the optic cup is spatially correlated with the location of most pronounced neuroretinal rim loss and visual field damage. Because high-pressure glaucoma is typically associated with optic cup deepening and vascular optic nerve damage is associated with optic cup flattening, the spatial correlation between focal optic nerve damage and focal cup deepening may suggest the presence of a pathogenetic aspect in both high-pressure glaucoma and focal normal-pressure glaucoma.     

Ranking of optic disc variables for detection of glaucomatous optic nerve damage

PURPOSE: To describe optic disc variables assessed by evaluation of clinical optic disc photographs and to compare sensitivity and specificity of these optic disc parameters in identifying patients with ocular hypertension who have nerve fiber layer defects and normal visual fields and patients with visual field defects. METHODS: The study included 500 normal subjects, 132 patients with ocular hypertension with retinal nerve fiber layer defects and normal visual fields (preperimetric glaucoma), and 840 patients with glaucomatous visual field defects. Color stereo optic disc photographs were morphometrically evaluated. RESULTS: Highest diagnostic power for the separation between the normal group and the preperimetric glaucoma group had the vertical cup-to-disc diameter ratio corrected for its dependence on the optic disc size, total neuroretinal rim area, rim-to-disc area ratio corrected for disc size, and cup-to-disc area ratio corrected for disc size. Diagnostic power was lower for rim area in the temporal inferior and temporal superior disc sector, cup area corrected for disc size, and horizontal cup-to-disc diameter ratio corrected for disc size. Less useful for the differentiation between the normal subjects and the preperimetric glaucoma group were size of zones alpha and beta of parapapillary chorioretinal atrophy, and ratios of neuroretinal rim width and rim area comparing various optic disc sectors with each other. CONCLUSIONS: In subjects with ocular hypertension with retinal nerve fiber layer defects and normal conventional achromatic visual fields, the vertical cup-to-disc diameter ratio corrected for optic disc size, total neuroretinal rim area, rim-to-disc area ratio, and cup-to-disc area ratio corrected for disc size are the most valuable optic disc variables for early detection of glaucomatous optic nerve damage. Correction for optic disc size is necessary for optic disc variables directly or indirectly derived from the optic cup. Parapapillary atrophy is less important in the early detection of glaucoma.     

Contrast sensitivity and pattern visual evoked potential in patients with glaucoma

Contrast sensitivity and pattern visual evoked potential (VEP) were measured in cases of ocular hypertension and primary open-angle glaucoma at various stages. The visual field of each eye was examined quantitatively and the retinal nerve fiber layer and optic disc were precisely assessed with magnified stereoscope fundus photography.This study revealed that contrast sensitivity of the eyes with glaucoma was within the normal range in the very early stage of the disease. As optic nerve damage advanced, high-or low-frequency loss developed. Further optic nerve damage produced a level type of loss.Pattern VEPs also showed increasing abnormalities as glaucomatous optic nerve damage progressed. Measurements of contrast sensitivity and pattern VEP were found not to be as sensitive as quantified precise visual field measurment or color stereosopic fundus photography for detection of minor optic nerve damage in cases of early glaucoma. These methods may be useful, however, as an objective and subjective monitor of progression of optic nerve damage in glaucoma.     

Distribution of axonal transport blockade by acute intraocular pressure elevation in the primate optic nerve head.

We studied the degree of axonal transport blockade in various areas of the optic nerve head with acute intraocular pressure (IOP) elevation in 19 squirrel monkey eyes. When IOP was raised to 20 to 50 mm. Hg for 7 hr., mild axonal transport blockade occurred in each area of the disk, most prominently in nerve fiber bundles of the superior pole. With 7 hr. IOP elevations between 50 and 90 mm. Hg, a somewhat greater degree of transport blockade occurred throughout the nerve head, although again the superior and inferior poles were somewhat more affected. The distribution of short-term transport blockade over the entire nerve head corresponds to the diffuse damage of acute glaucoma, but the pattern hints at the preference for damage near the poles of the disk seen in chronic glaucoma. However, before these results can be fully evaluated, further information is needed on axonal pathways through the optic nerve head and on the relationship between transport obstruction and ganglion cell death.     

Parapapillary retinal vessel diameter in normal and glaucoma eyes. I. Morphometric data

The retinal blood vessels serve for nutrition of the retinal ganglion cells and their axons. This study was undertaken to evaluate the vessel diameter in normal and glaucoma eyes. The calibers of the superior temporal and inferior temporal retinal artery and vein were measured at the optic disc border and at a distance of 2 mm from the optic disc center; 473 eyes of 281 patients suffering from chronic primary open-angle glaucoma and 275 eyes of 173 normal subjects were examined. Fifteen-degree, color stereo optic disc photographs were used. In the normal eyes the inferior temporal vessels were significantly larger than the superior temporal vessels. This corresponds with: (1) the configuration of the normal neuroretinal rim, which is significantly broader in the inferior disc region than in the superior disc area; (2) the visibility of the retinal nerve fibers, which are better detectable in the inferior temporal area than in the superior temporal one; and (3) the foveola location 0.53 +/- 0.34 mm inferior to the optic disc center. The retinal vessel diameter was independent of the patients' age and optic disc and parapapillary chorioretinal atrophy size. In the glaucoma group the vessel caliber was significantly smaller than in the normal eyes. The differences were more marked for the arteries and the inferior temporal vessels, respectively. The vessel diameters decreased significantly with increasing glaucoma stage independently of the patients' age. The parapapillary retinal vessel diameter may reflect the need of vascular supply in the corresponding superficial retinal area. It may be correlated with the local ganglion cell density and retinal nerve fiber layer thickness.     

An analysis of visual acuity, visual fields, and disk cupping in childhood glaucoma

We analyzed the long-term functional results in 102 eyes of 59 patients with childhood glaucoma with specific reference to the pattern of optic nerve damage. Optic disk photography and quantitative perimetry were used to judge the degree of damage that had been sustained. There was a predilection for initial visual field damage in the arcuate area, followed by further arcuate and nasal field loss, similar to the pattern of visual field loss seen in adult glaucoma. In children, as in adults, neural tissue appeared to be lost preferentially at the vertical disk poles. The selective pattern of glaucomatous optic nerve damage seemed not to depend upon the age of the optic nerve structures. In contrast to adult eyes, the scleral canal in children apparently enlarges with high IOP. Thus, disk cup size increase in children could occur from neural tissue loss, from scleral canal enlargement, or from a combination of the two processes.     

Measurement of relative nerve fiber layer surface height in glaucoma

A new parameter of structural optic nerve damage from glaucoma is reported, the relative nerve fiber layer surface height (RNFLH). Relative nerve fiber layer surface height is calculated from magnification-corrected surface contour measurements of the peripapillary retina made with computerized image analysis of stereoscopic videographic images. The technique measures the average height of the nerve fiber layer surface within a circumference 200 microns from the disc edge, as detected with narrow-band green light, with respect to a standardized reference plane. This parameter was examined in a group of 36 glaucoma patients with early to moderate visual field loss, and in 33 age-matched normal controls. The measured surface of the peripapillary nerve fiber layer was, on the average, 74 microns lower in glaucomatous eyes than in normal eyes, a statistically significant difference (P = 0.000). The ability of RNFLH to distinguish glaucomatous eyes from normal eyes was tested by its sensitivity (83%) and specificity (88%), which were greater than the sensitivities and specificities of computerized measurements of cup-disc ratio, disc rim area, and cup volume. This approach represents a step toward the identification of quantitative structural parameters to reflect the number of retinal ganglion cell axons that enter the optic nerve. Such measurements may facilitate the early diagnosis of glaucoma and provide important information on rates of ganglion cell death in aging and disease.     

Bilateral visual field defects with optic disc drusen and secondary open angle glaucoma with PEX--clinical correlation with the HRA

BACKGROUND: Arcuate visual field defects are a typical sign of glaucomatous damage. Elevated intraocular pressure in combination with pseudoexfoliation syndrome (PSX) manifests the diagnosis glaucoma. Beyond this state, in microdiscs with optic disc drusen, the exact classification of the visual field defects is crucial. CASE REPORT: A 57-year-old male with pseudoexfoliation glaucoma was referred because of progressive glaucomatous visual field defects. The visual acuity was right 20/40 and left 20/25. Maximum intraocular pressure was 36 mm Hg. A simple optic nerve atrophy was diagnosed superonasally. The optic disc size was OD 2.24 mm(2) and OS 1.89 mm(2) (HRT I). An Ultrasound B-mode scan demonstrated the diagnosis of optic disc drusen. Over a follow-up of 1 year, a growth tendency was observed, especially in the superonasal quadrant. The mulberry-shaped surface of the drusen was visualized with infrared reflection images (HRA II, 830 nm). Confocal scanning laser ophthalmoscopy (HRA II, excitation 488 nm, 500 nm notch filter) showed an increased intrapapapillary autofluorescence (> 50 % papillary area: OD 1.67 mm(2), OS 1.26 mm(2)). This technique could detect drusen in areas that looked normal in classical retinoscopy. CONCLUSION: The differential diagnosis of arcuate scotomas includes simple optic nerve atrophy and glaucomatous optic nerve atrophy. Optic disc drusen in glaucoma eyes can obscure the main cause of progressive visual field loss. Superficial optic disc drusen can be measured planimetrically over the years. An adequate reduction of intraocular pressure should be realized in these eyes.     

Chronic glaucoma selectively damages large optic nerve fibers

To determine whether glaucoma selectively injures a particular size of optic nerve fiber (and its cell body), we induced chronic experimental glaucoma in one eye each of ten monkeys. With automated image analysis, the number and diameter of optic nerve fibers were compared between each glaucomatous eye and its normal fellow eye. Fibers larger than the normal mean diameter atrophied more rapidly in glaucomatous eyes, though no fiber size was spared from damage. The mean fiber diameter for glaucomatous eyes was 0.74 micron, significantly lower than the mean for ten fellow eyes, 0.85 micron (P less than 0.005). There was preferentially greater atrophy of fibers of all sizes in the superior and inferior peripheral nerve sectors, as seen in human eyes with glaucoma. The more rapid atrophy of larger fibers appeared to result from two causes. The areas that suffer most rapid loss of fibers in experimental glaucoma normally contain a high proportion of larger diameter fibers. Furthermore, larger fibers were lost preferentially even in areas of the optic nerve with mild damage, indicating their inherent susceptibility to injury by glaucoma. The tendency for large fibers to be lost in glaucoma has implications for future improvements in testing for early glaucoma damage.     

Polarimetric measurement of retinal nerve fiber layer thickness in glaucoma diagnosis

PURPOSE: To evaluate reliability and diagnostic value of polarimetric measurements of the retinal nerve fiber layer (RNFL) thickness in the diagnosis of glaucoma. METHODS: The study included 81 eyes with perimetric glaucoma with glaucomatous changes of the optic disc and visual field defects; 52 eyes with preperimetric glaucoma with glaucomatous optic disc abnormalities and normal achromatic visual fields; and 70 normal eyes. For determination of reliability, four examiners repeated polarimetric measurements five times in ten normal subjects. RESULTS: The polarimetric variables were significantly correlated with increasing mean visual field defect and decreasing neuroretinal rim area. In correlation analyses with visual field defects, correlation coefficients were highest for the variable "superior/nasal ratio" and "the Number," a variable calculated by the neural network of the device. In correlations with neuroretinal rim area, correlation coefficients were highest for measurements of the inferior nerve fiber layer thickness. The preperimetric glaucoma group and the control group differed significantly in the variables "superior/nasal ratio" and "the Number" and, to a smaller degree, in the variables "superior/temporal ratio" and "superior/inferior ratio." The Number variable had a sensitivity of 82% and 58% at a predefined specificity of 80% in separating perimetric glaucoma patients and preperimetric glaucoma patients, respectively, from control subjects. Reproducibility of the polarimetric measurements ranged between 70% and 89%. CONCLUSION: Polarimetric measurements of the RNFL thickness can detect glaucomatous optic nerve damage in patients with visual field loss, and in some patients with preperimetric glaucomatous optic nerve damage. Considering the fast performance, easy handling, and low maintenance costs, RNFL polarimetry may be helpful in glaucoma diagnosis.     

HRT在青光眼与近视眼中的研究

青光眼是以进行性视神经损害为特征的不可逆性致盲眼病,其病理基础是视网膜神经节细胞及其纤维的进行性丧失;近视眼是开角型青光眼的易患因素,合并近视的青光眼患者其检查结果又有自身的特点,这给我们早期的准确诊断增加了难度;HRT是一种自动化的电子计算机控制的共焦激光眼底断层扫描仪。利用HRT(heidelberg retinatom ograph)可以获取视盘的三维地形图,通过对图像的分析处理,得到视盘和视网膜神经纤维层厚度的定量描述,并且可用于地形图变化的定量分析。本文就HRT在青光眼和近视眼特别是近视合并青光眼中的诊断和在视神经损害监测中的研究作一综述。     

Optic disc size and optic nerve damage in normal pressure glaucoma.

BACKGROUND--Recent reports indicate that eyes with normal pressure glaucoma have larger optic discs than eyes with primary open angle glaucoma or normal eyes. This study was performed to find whether, in normal pressure glaucoma, a large disc is associated with more optic nerve damage than a small disc. METHODS--Colour optic disc photographs of 74 patients with normal pressure glaucoma were assessed morphometrically. RESULTS--Taking the study group as a whole, the optic disc size decreased significantly (p = 0.04) with increasing visual field defect. In an intraindividual bilateral comparison, the side differences in the disc area of the right minus the left eye of the same individual were not significantly correlated with the side differences in the mean visual field defect. CONCLUSIONS--The results indicate that the eye with the larger optic disc, when compared with the contralateral eye with the smaller optic nerve head, showed neither a significantly more marked nor less pronounced glaucomatous optic nerve damage. It suggests that for a given patient the degree of glaucomatous optic nerve atrophy was not markedly associated with the optic disc size. The finding that patients with large visual field defects had smaller discs than patients with moderate perimetric loss may indicate that the results of previous cross sectional studies reporting on an unusually large disc size in normal pressure glaucoma may be due partially to selection.     

HRT视盘参数在原发性开角型青光眼早期诊断中的作用

目的:在众多海德堡视网膜断层扫描仪(heidelberg retina tomogragh,HRT)测定的视盘参数中,筛选出最有助于青光眼早期诊断的视盘参数。方法:用HRT测定23例视野损害较轻的青光眼患者和23例正常人的视盘参数(杯盘面积比、盘沿面积、盘沿容积、视杯容积、视杯形态测量、视杯高度变异轮廓和平均神经纤维层厚度)作逐步判别分析。结果:盘沿面积和杯盘面积比对青光眼早期诊断最有帮助,其诊断敏感度和特异度分别为87%和96%。结论:本组资料盘沿面积和杯盘面积比是区分青光眼和正常眼最好的判别因素。     

青光眼视神经损伤机制的研究进展

青光眼是目前全球范围内致盲性最高的疾病之一,是以进行性视网膜神经节细胞丧失、不可逆的视野损害等病理性改变为特征,最终导致视神经萎缩及视功能丧失的疾病。目前青光眼的发病机制并不完全清楚,其中视神经损伤的机制有多种学说,包括眼压因素及非眼压因素,非眼压因素包括血管因素、免疫作用、远端轴突病变、氧化应激作用、细胞因子的变化及自噬等机制。本文综述了有关青光眼视神经损伤机制的研究进展,为进一步研究青光眼视神经病变提供依据。     

Preperimetric glaucoma diagnosis by confocal scanning laser tomography of the optic disc

AIM: To evaluate the ability of confocal scanning laser tomography of the optic nerve head to detect glaucomatous optic nerve damage in ocular hypertensive eyes without visual field defects. METHODS: The study included 50 normal subjects, 61 glaucoma patients with glaucomatous changes in the optic disc and visual field, and 102 "preperimetric" patients with increased intraocular pressure, normal visual fields, and glaucomatous appearance of the optic disc as evaluated on colour stereo optic disc photographs. For all individuals, confocal scanning laser tomographs of the optic nerve head were taken using the Heidelberg retina tomograph (HRT; software 2.01). RESULTS: Almost all investigated HRT variables varied significantly (p < 0.05) between the normal eyes and preperimetric glaucoma eyes with pronounced overlap between the two study groups. Corresponding to the overlap, sensitivity and specificity values were relatively low when HRT variables were taken to differentiate between normal and preperimetric glaucoma eyes. At a given specificity of 95% highest sensitivities were found for the variables "rim area in the superior disc sector" (24.8%), "nerve fibre layer thickness in the inferior disc sector" (26.5%), and "rim volume in the superior disc sector" (25.5%). A multivariate approach increased sensitivity to 42.2% at a given specificity of 95%. For the glaucoma group highest sensitivity values were reached by rim volume in the superior disc sector (73.8%) and rim area (72.1%); the multivariate approach reached 83.6%. CONCLUSIONS: Owing to pronounced overlapping between the groups, confocal scanning laser tomography of the optic nerve head has relatively low diagnostic power to differentiate between normal eyes and preperimetric glaucoma eyes. One of the reasons may be the biological interindividual variability of quantitative optic disc variables.     

Quantitative evaluation of the optic nerve head in patients with unilateral visual field loss from primary open-angle glaucoma

Measurable structural alterations of the optic nerve head may precede visual field abnormalities in early open-angle glaucoma. The authors studied the optic nerve heads of 10 patients with unilateral visual field loss from primary open-angle glaucoma, and 12 age- and sex-matched normal subjects. Topographic optic nerve head parameters were measured with a system of computerized image analysis (Rodenstock Analyzer, G. Rodenstock Instrumente GMBH, Munich, W. Germany). In patients with asymmetric primary open-angle glaucoma, eyes with normal visual fields had a slightly larger mean (+/- standard error of the mean) disc rim area (0.90 +/- 0.04 mm2) than eyes with glaucomatous visual field defects (0.78 +/- 0.05 mm2). However, both sets of eyes in the asymmetric primary open-angle glaucoma patients had smaller mean disc rim areas (P less than 0.0007) than did the control group (1.27 +/- 0.09 mm2). These findings support the hypothesis that loss of the optic disc rim can be detected before perimetric abnormalities develop in primary open-angle glaucoma.