Evaluation of the retinal nerve fiber layer in glaucoma

The health of the optic nerve in glaucoma can be evaluated by examination of the retinal nerve fiber layer with red free illumination. Retinal nerve fiber layer defects have been shown in some studies to precede enlargement of optic cupping and visual field defects in glaucoma patients. Detection of glaucomatous damage at an earlier stage in the disease may prevent subsequent visual field loss. Retinal nerve fiber layer evaluation may give important information in the management and treatment of glaucoma patients.     

Initial glaucomatous optic disk and retinal nerve fiber layer abnormalities and their progression

We attempted to identify the initial glaucomatous changes of the optic disk and retinal nerve fiber layer and to analyze how these changes subsequently progressed. Of 61 eyes of 61 patients with ocular hypertension, 23 (38%) developed glaucoma during ten years of follow-up (range, five to 15 years). The initial sign of glaucomatous damage was diffuse enlargement of the optic disk cup in ten of 23 eyes or generalized thinning of the nerve fiber layer without localized changes in 12 of 23 eyes. We found localized optic disk damage in ten of 23 patients and localized retinal nerve fiber layer damage in 11 of 23 patients alone or in combination with diffuse damage. In 13 of 23 eyes, the cupping ended up in diffuse enlargement with even more profound thinning of the neural rim in the upper and lower temporal disk margins. There seems to be great variability in the appearance and progression of the initial glaucomatous optic disk and nerve fiber layer abnormalities in patients with increased intraocular pressure.     

Measurement of peripapillary retinal nerve fiber layer volume in glaucoma

PURPOSE: To measure peripapillary retinal nerve fiber layer volume in normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. METHODS: Sixty-five subjects were classified into four groups of normal subjects and subjects with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma on the basis of intraocular pressure measurements, visual field loss, and optic disk appearance. Groups were matched for sex, age, and optic disk area. Peripapillary retinal nerve fiber layer volume measurements were made with a modification of software version 1.11 of the Heidelberg Retina Tomograph confocal scanning laser ophthalmoscope. Retinal nerve fiber layer volume measurements were taken at 0.1-mm increments from the disk margin for a global 360-degree assessment and at four predefined segments using two different reference planes. Statistical analysis was carried out using analysis of variance with Bonferroni correction. RESULTS: Retinal nerve fiber layer volume measurements showed a gradation from normal to ocular hypertension and from ocular hypertension to glaucoma groups. Mean group measurements showed statistically significant differences (P <.05) in peripapillary retinal nerve fiber layer volume for most segmental measures between the groups. Measurements with the default reference plane in the 0.0-mm to 0.1-mm and 0.1-mm to 0.2-mm increments for the superotemporal segment showed the greatest differences between groups (P <.00005). CONCLUSION: Peripapillary retinal nerve fiber layer volume measurements differ between groups of normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. This measure offers a further method of assessment of retinal nerve fiber layer in patients with glaucoma and glaucoma suspects.     

Glaucoma without cupping.

BACKGROUND: Although glaucoma can exist with normal intraocular pressures (IOPs), clinicians still rely on the presence of a large cup to "flag" suspects, regardless of IOP, whereas a small cup at the same pressure level is often ignored. High-tech instruments offer a new dimension of evaluation in the objective assessment of structure when subjective tests of function and/or ophthalmoscopic observations are equivocal. CASE REPORTS: Thirteen cases are presented and show evidence of glaucoma based on glaucomatous visual-field defects, often with steadily rising intraocular pressures and retinal nerve fiber layer loss. Surprisingly, these patients maintained small C/D ratios. Accordingly, ophthalmoscopy and/or disk topography classified these disks as normal. CONCLUSIONS: Although unrecognized in virtually the entire world's ophthalmic literature, normal cup glaucoma is a real clinical entity. At least half the normal cup glaucoma cases presented herein have disk drusen (obvious, subtle, or occult), while others are highly myopic and/or have documented IOP spikes. Several of the cases defy classification and explanation at the present time.     

Optic nerve head appearance in juvenile-onset chronic high-pressure glaucoma and normal-pressure glaucoma

OBJECTIVE: To evaluate the appearance of the optic nerve head in chronic high-pressure glaucoma and normal-pressure glaucoma. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: The study included 52 eyes with normal-pressure glaucoma and 28 eyes with juvenile-onset primary open-angle glaucoma that served as models for chronic high-pressure glaucoma. METHODS: Color stereo optic disc photographs and wide-angle retinal nerve fiber layer photographs were morphometrically examined. MAIN OUTCOME MEASURES: Localized retinal nerve fiber layer defects; parapapillary chorioretinal atrophy; disc hemorrhages; optic cup shape; retinal arteriole narrowing. RESULTS: Both study groups did not vary significantly in count of localized retinal nerve fiber layer defects, size of parapapillary atrophy, optic cup depth, steepness of disc cupping, rim/disc area ratio, diameter of retinal arterioles, and frequency and degree of focal retinal arteriole narrowing. In normal-pressure glaucoma versus juvenile open-angle glaucoma, localized retinal nerve fiber layer defects were significantly broader, disc hemorrhages were found significantly more often and were larger, and neuroretinal rim notches were present more frequently and were deeper. CONCLUSIONS: Chronic high-pressure glaucoma and normal-pressure glaucoma show morphologic similarities in the appearance of the optic nerve head. The lower frequencies of detected disc hemorrhages and rim notches in high-pressure glaucoma may be due to a smaller size of hemorrhages and localized retinal nerve fiber layer defects in high-pressure glaucoma. Both glaucoma types have morphologic features in common, suggesting that they may possibly belong to a spectrum of the same pathologic process.     

Glaucomalike disks without increased intraocular pressure or visual field loss

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.     

Diagnosing glaucoma progression: current practice and promising technologies

PURPOSE OF REVIEW: An update on recent work is provided that has broadened our understanding of the evaluation of visual function and structure, and their use in evaluating glaucoma progression. RECENT FINDINGS: The challenge of determining visual-field progression and the implications of long-term fluctuation are reviewed and data to support the magnitude of the fluctuation are cited. The use of confirmatory testing can limit the over diagnosis of glaucoma progression. Focusing visual-field testing on the locations of present scotomas or using frequency doubling technology may provide new approaches to assessing visual function. New standardized techniques to interpret visual fields, including neural networks, unsupervised machine learning and pointwise linear regression, may provide more quantitative means for visual-field interpretation. These techniques, along with structural evaluation of the optic nerve and nerve fiber layer, are essential in glaucoma management. Optic-nerve-head photography is still a mainstay in evaluating glaucoma progression, although many technologies including scanning laser tomography, scanning laser polarimetry and optical coherence tomography offer more quantitative means to follow structural change. These modalities, in different ways, show promise in providing additional information regarding the stability of glaucoma. SUMMARY: Identifying the functional visual component as well as structural changes is essential in evaluating glaucoma progression. New techniques of testing and evaluating visual fields, the optic-nerve head, and the retinal nerve fiber layer offer exciting opportunities to more accurately identify glaucoma progression, and are likely to become more central as imaging devices and software support develop further.     

Correlation among retinal thickness,optic disc,and visual field in glaucoma patients and suspects: a pilot study

OBJECTIVE: To correlate losses of retinal thickness in the perifoveal area in glaucoma as measured by the Retinal Thickness Analyzer (Talia Technology Ltd, Israel) with optic nerve and visual field changes in glaucoma patients and suspects. METHODS: Observational case series of 55 consecutive patients from the Glaucoma Service who either presented with a diagnosis of glaucoma or were referred for evaluation of suspected glaucoma. The Retinal Thickness Analyzer (Talia Technology, Ltd.) was used to obtain retinal thickness maps. Retinal thickness analysis, visual field testing, and stereophotography of the optic nerve head were performed, and a glaucoma specialist who was masked to patient status and identity data randomly graded the level of severity of each parameter. Spearman rank correlations were used to assess the relationships among the three numerical measures. RESULTS: Retinal thickness losses correlated more strongly with severity of optic nerve head cupping (r = 0.75), whereas both of these measures correlated less strongly with the severity of visual field loss (r = 0.54). CONCLUSIONS: Retinal thickness measurements at the posterior pole provide another measure of neural loss in glaucoma, and may help in the clinical assessment of optic nerve cupping. However, there are limitations of the technology that must be considered.     

Relationship between structural abnormalities and short-wavelength perimetric defects in eyes at risk of glaucoma

PURPOSE: To determine the relative prevalence of blue-yellow perimetric defects and structural abnormalities of the optic nerve and nerve fiber layer in eyes at risk of glaucoma. METHODS: Seventy-two eyes (of 72 patients) at risk of glaucoma, with normal white-on-white full threshold perimetry, were examined prospectively with blue-yellow full-threshold perimetry (Humphrey). Structural evaluations were conducted with qualitative assessment of stereoscopic color optic disk photographs and monochromatic nerve fiber layer photographs performed independently by three masked examiners (a glaucoma specialist and two glaucoma fellows), and statistical analysis of summary parameters was obtained with scanning confocal laser tomography (abnormal defined as values outside 95% confidence limits established in normal control subjects). RESULTS: Kappa values for interobserver agreement were 0.64, 0.88, and 0.79 for optic disk evaluation and 0.59, 0.60, and 0.61 for nerve fiber layer evaluation. Thirteen (18%) of 72 eyes had blue-yellow abnormalities. A total of 30 eyes (42%) were identified as having a structural abnormality; 29 (40%) had qualitatively determined optic disk abnormalities, 21 (29%) had qualitatively determined nerve fiber layer defects, and 26 (36%) had statistically significant structural abnormalities. Twelve of 13 eyes with blue-yellow defects had a detectable structural abnormality; all 12 had abnormalities identified with disk photography, nine with nerve fiber layer photography, and 12 by scanning laser tomography. CONCLUSIONS: Clinically detectable structural abnormalities frequently coexist with blue-yellow perimetric defects in patients with ocular hypertension. A substantial proportion of patients with ocular hypertension with normal blue-yellow perimetry has early detectable glaucomatous structural abnormalities.     

Wedge-shaped retinal nerve fiber layer defects in experimental glaucoma preliminary report

Many investigators have reported that abnormalities in the retinal nerve fiber layer may be the earliest sign of primary open-angle glaucoma. We attempted to create defects in the retinal nerve fiber layer in experimentally induced glaucoma and to examine their histology. By repeated circumferential argon laser photocoagulation of the trabecular meshwork of normal cynomolgus monkeys, we succeeded in causing a continuous increase in intraocular pressure (IOP). During the course of this experiment, cupping of the optic nerve head, wedge-shaped retinal nerve fiber layer defects, and halo glaucomatosus developed, all of which are defects that are similar to those seen clinically in primary open-angle glaucoma. The IOP required for this fundus change was 25, 35, and 43 mmHg, indicating great individual variation. Histological examination revealed localized degeneration, loss of axon bundles, and diffuse thinning of the nerve fiber layer in the area of these wedge-shaped defects in the retinal nerve fiber layer. These results may indicate that the optic-nerve-damaging mechanism, both localized and generalized, is the same in the cynomolgus monkey and in man.     

Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys

PURPOSE: To evaluate the retinal tolerance time to acute ischemic insult in middle-aged or elderly rhesus monkeys with pre-existing atherosclerosis and arterial hypertension. METHODS: In 39 eyes of 39 middle-aged and elderly rhesus monkeys with a mean age of 19.5 +/- 2. 8 years, occlusion of the central retinal artery was produced by temporary clamping of the central retinal artery at its site of entry into the dural sheath of the optic nerve for 97 to 300 minutes. Stereoscopic color fundus photography and fluorescein fundus angiography were performed before central retinal artery occlusion and serially thereafter. Retinal nerve fiber layer damage and optic disk changes were assessed by comparing morphometric evaluation of the color fundus photographs taken before central retinal artery occlusion and color fundus photographs taken at the end of the study. RESULTS: There was a significant correlation between duration of central retinal artery occlusion and decreased visibility of retinal nerve fiber layer (P =.018) and increasing optic disk pallor (P =. 014), and a trend between residual retinal circulation and decreased visibility of retinal nerve fiber layer (P =.085) and optic disk pallor (P =.162). However, there was a marked interindividual variation between the length of central retinal artery occlusion and degree of increased optic disk pallor and decreased visibility of the retinal nerve fiber layer, even among eyes with similar duration of central retinal artery occlusion. Complete or almost total optic nerve atrophy and nerve fiber damage were present in all eyes in which the duration of central retinal artery occlusion was 240 minutes or more. CONCLUSIONS: The findings of this study, compared with our previous study in young healthy rhesus monkeys, indicate that in middle-aged or elderly atherosclerotic and arterial hypertensive rhesus monkeys, central retinal artery occlusion for less than 100 minutes produced no apparent morphometric evidence of optic nerve damage; however, central retinal artery occlusion of 105 minutes but less than 240 minutes produced a variable degree of damage; central retinal artery occlusion for 240 minutes or more produced total or almost total optic nerve atrophy and nerve fiber damage.     

准分子激光原位角膜磨镶术眼压的变化和术后青光眼的诊断

准分子激光原位角膜磨镶术（laser in situ keratomileusis,LASIK）是矫正近视最常用的手术方式,术中和术后引起的眼压的变化和术后青光眼的诊断应当引起注意.术中形成的眼压升高,对视盘和视网膜造成潜在的危害.术后中央角膜变薄,导致眼压测量值偏低,易发生青光眼的漏诊.术后长期应用糖皮质激素药物可能引起角膜瓣下层间积液和继发性青光眼.视盘和视网膜神经纤维层检查可能对早期青光眼诊断提供一些参考.     

Morphometric characteristics of optic disk with disk hemorrhage in normal-tension glaucoma.

PURPOSE: To evaluate the morphometric characteristics of the optic disk in eyes with and without disk hemorrhage in normal-tension glaucoma. METHODS: This was a prospective study conducted at Gifu University Hospital of 50 eyes of 50 patients with normal-tension glaucoma (12 men, 38 women; age, 56.5 +/- 14.1 years) who had developed new disk hemorrhage at the time of enrollment and 58 eyes of 58 patients with normal-tension glaucoma (20 men, 38 women; age, 56.7 +/- 12.4 years) with no history of disk hemorrhage during the follow-up period of more than 2 years. Age and global indexes of the visual field were matched. We morphometrically compared the optic disk with and without hemorrhage using a scanning laser tomograph. Global and sector analyses were made of the optic disk structural parameters. RESULTS: There was no significant difference in the global values of the disk parameters between the disk hemorrhage and the nonhemorrhage groups. However, the inferotemporal values for the rim area, rim volume, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area in the disk hemorrhage group were significantly smaller than those in the nonhemorrhage group (P <.05). In the disk hemorrhage group, moreover, the values for the rim area, rim volume, and retinal nerve fiber layer cross-section area in the inferotemporal sector with hemorrhage were significantly smaller than those in the same sector without hemorrhage (P <.05). CONCLUSION: Localized damage of the disk rim and retinal nerve fiber layer at the inferotemporal sector was prominent in eyes with disk hemorrhage.     

Relationship of optic disk topography and visual function in patients with large cup-to-disk ratios

PURPOSE: To determine if topographic differences exist between large cup-to-disk ratio (C/D) eyes with standard achromatic automated perimetry (SAP) abnormalities and those with only short-wavelength automated perimetry (SWAP) abnormalities. DESIGN: Cross-sectional study. METHODS: The setting was a referral university-based clinical practice. We selected one eye of 72 patients with a vertical C/D of at least 0.8 by ophthalmoscopy. Patients performed SWAP, SAP, and confocal scanning laser ophthalmoscopy. We compared optic disk topography in eyes with and without visual field abnormalities and controlled for the influence of disk area. RESULTS: Disk area was a confounder of many topographic measures. After controlling for disk area, eyes with abnormal SAP had differences in rim volume, cup shape, rim area, retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-sectional area when compared with eyes with normal SAP (P <.05). Rim volume and rim area were different in the SWAP comparison (P <.05). CONCLUSIONS: Investigators should control for disk area when evaluating topographic measures by confocal scanning laser ophthalmoscopy. In eyes with a large C/D, optic disk topography is more glaucomatous in eyes with SAP abnormalities than in those with only SWAP abnormalities. Eyes with large C/D and only SWAP abnormalities may have fewer glaucomatous optic disk changes than such eyes with SAP abnormalities. This indicates that SWAP is likely to correspond to abnormalities in optic disk topography at an earlier stage of glaucomatous optic neuropathy than SAP. Therefore, clinicians should consider SWAP testing in glaucoma suspects to detect glaucomatous visual field loss at an earlier stage of structural loss.     

Correlation of the optic disc size to glaucoma susceptibility

Previous studies have suggested that a larger optic disc size in blacks as compared with whites is related to the increased glaucoma susceptibility in blacks. In an intraindividual bilateral comparison of 245 white patients with open-angle glaucoma, the authors evaluated whether the glaucomatous optic nerve damage was greater or less in the eye with the larger optic nerve head. Highly myopic eyes were excluded. The difference in optic disc area of one eye as compared with the contralateral eye was not significantly correlated to the differences in visibility of retinal nerve fiber bundles and mean visual field defect between the two eyes. Mean perimetric loss and the retinal nerve fiber layer index were not significantly higher in the eye with the larger or smaller optic nerve head. This indicates that in whites, high myopes excluded, the susceptibility to glaucomatous optic nerve fiber loss may be independent of the optic disc size.     

Experimental alphachymotrypsin glaucoma.

Experimental glaucoma was produced in 50% of rabbit eyes by injecting 75 units of alphachymotrypsin into the posterior chamber. The elevation of intraocular pressure was stable, rarely exceeded 50 mm Hg, and lasted one year or longer. Progressive buphthalmos first appeared 2 to 3 weeks following injection of the enzyme. Ocular histologic changes included bullous keratopathy, iris and ciliary body atrophy, and cupping of the optic disc. The optic nerve became atrophic but no cavernous degeneration occurred. In the retina there was thinning of the nerve fiber layer and loss of ganglion cells with preservation of the other retinal elements. The mechanism leading to glaucoma following alphachymotrypsin injection is unclear. This study demonstrated formation of peripheral anterior synechiae and reduction of outflow facility within 2 weeks following injection and these factors may play a role.     

Papillenfotografie und retinale Nervenfaserschichtfotografie

In addition to optic disc assessment at the slit lamp and the use of imaging devices for glaucoma diagnosis, optic disc photography is widely used in clinical practice. The advantages of stereophotography are a permanent recording of the optic disc status especially used for serial evaluation of discs, good visibility of the peripapillary region and a relatively fast examination without pupil dilation (if using non-mydriatic fundus cameras). The limitations are the need for clear media, pupil dilation, a skilled photographer and the delay involved. Retinal nerve fiber layer (RNFL) photography is based on the absorption of green light by melanin in the retinal nerve fiber layer. In comparison to scanning laser devices this methodology is not as convenient and requires widely dilated pupils and high levels of competence by technical personnel. Furthermore, the examination with RNFL photographs requires considerable learning and experience. RNFL photography detects glaucoma damage before visual field defects occur.     

Early detection of glaucomatous damage. II. Changes in the appearance of the optic disk

Once we understand that an increase in the size of the optic disk cup is due to loss of optic nerve fibers combined with some physical tissue rearrangements, it is quite clear that cupping begins as soon as nerve loss begins. Methods to detect cupping are more sensitive to the earliest glaucoma damage than are present field testing methods. This conclusion is supported by large clinical studies and histological demonstration of nerve fiber loss prior to field loss in eyes with abnormal cups, asymmetric cupping, or nerve fiber layer abnormalities. While automated perimetry is likely to increase the sensitivity of detection, better test methodologies are needed to combine with the objectivity of computer-assisted machines. Disk hemorrhages, nerve fiber layer defects, and color vision abnormalities are early signs of damage, supporting the conclusion that damage is present before field loss. A number of other methods await further testing to determine their effectiveness. The idea that the disease glaucoma is defined by a certain visual field finding on the Goldmann perimeter is not valid if we define glaucoma as an eye with a history of elevated IOP and optic nerve damage. While such field loss is a convenient means of defining a particular stage of damage in glaucoma, there are clearly earlier stages of damage, whether we can always detect them or not. No patient should be told that he or she does not have glaucoma, but rather has ocular hypertension, based on a particular visual field finding. As testing and examination methods improve, so, hopefully, will our ability to determine whether damage is present. As this occurs, we will be better enabled to select most rationally those patients who will benefit from therapy. The idea that field testing is relatively insensitive to the earliest glaucoma damage might lead the skeptic to conclude that perimetry is not worth the trouble. This review has indicated that none of our present methods, ophthalmoscopic, psychophysical or otherwise, is perfect. But to omit using any of them (especially field testing) does a great disservice to the glaucoma patient. The greatest usefulness of the new automated instruments is that adequate field testing is now available in a cost-effective form to every ophthalmic office. We need to strive for better detection and follow-up of glaucoma damage to prevent needless blindness.     

The diagnostic value of optic nerve imaging in early glaucoma

In the last decade, new imaging techniques have been added to conventional fundus photography and have been evaluated for use in early glaucoma. They all measure the loss of neuroretinal rim or retinal nerve fiber layer as a correlate to glaucomatous ganglion cell and axon loss. The value of optic disc photography, planimetry, laser scanning tomography, laser scanning polarimetry, and optical coherence tomography for the diagnosis of glaucomatous eyes in a preperimetric or early perimetric stage is analyzed on the basis of sensitivity, specificity, and receiver operating characteristics (ROC) curves. It becomes clear that all these techniques allow a more or less semi-automated evaluation of the optic disc and retinal nerve fiber layer but still have their limitations in the diagnosis of a very early, preperimetric stage of the glaucoma disease.