Glaucomatous Optic Nerve Damage Research Articles

3D vs 2D qualitative and semiquantitative evaluation of the glaucomatous optic disc atrophy using computer-assisted stereophotography

Real colour documentation of the optic nerve head (ONH) is one of the most important methods to identify the early progression of glaucomatous optic nerve damage. This study compares the qualitative and semiquantitative evaluation of ONH photographs, using a 3D time-multiplexing system and conventional 2D photography, visualised on a computer monitor. Stereophotographs of the ONH were converted by special software in a 3D file. The same images were shown in 2D and 3D to 22 subjects with different training grades (residents and ophthalmologists). The evaluation based on a standardised questionnaire, containing semiquantitative parameters of the ONH. A weighted score for quality of ONH assessment counted the correct answers of the observers to compare their evaluation in 2D to the one made in 3D. All of the observers achieved a significant better evaluation of the ONH with 3D than with 2D images. No significant differences were observed between both groups. Classification errors with respect to the 'gold standard' were lower for 3D measurements as compared with 2D measurements (P=0.007). No significant differences were observed between the gold standard and residents or ophthalmologists for the ONH size, but for the c/dratio the stereoscopic images lead to better results. This study showed a better evaluation of parameters associated with the glaucomatous ONH atrophy with 3D images compared with 2D, independent of the clinical training grade. The computer-based evaluation of the ONH atrophy by using a time-multiplexing system (shutter-glasses) may improve the diagnosis of glaucoma patients.

Frequency Doubling Perimetry and Short-Wavelength Automated Perimetry to Detect Early Glaucoma

To compare the ability of short-wavelength automated perimetry (SWAP) and frequency doubling perimetry (FDP) to detect early glaucoma damage. Prospective case-control study using a comparative case series. Forty-two patients with preperimetric glaucomatous optic nerve damage and a normal standard achromatic perimetry (SAP) in 1 eye, but with contralateral SAP abnormalities, and 35 normals. Forty-two patients and 35 normals underwent SWAP and FDP (Humphrey 24-2; Carl Zeiss Meditec, Inc., Dublin, CA). Correlations of mean deviation (MD) and pattern standard deviation (PSD) of the 2 groups were calculated. The number of defects at P<0.05 and P<0.01 on total deviation (TD) and pattern deviation (PD) plots were compared. Diagnostic precision and agreement on location of abnormalities were determined. Correlations and comparisons of global indices between SWAP and FDP: MD, PSD, TD, and PD abnormal number of points. Significant correlations in the glaucoma group were found between SWAP and FDP for MD (r = 0.54; P<0.008) and PSD (r = 0.49; P<0.001). Defects on the TD and PD plots were detected more frequently by FDP in the glaucoma group, although they were significant only for PD at P<0.01 (P = 0.024). Areas under receiver operator characteristic curves for MD of SWAP and PSD of FDP were 0.74 and 0.67, respectively (P = 0.37). Using defined defect criteria, FDP had a significantly higher sensitivity (72% vs. 54%; P = 0.02) and similar specificity (53% vs. 44%; P = 0.12) compared with SWAP. Agreement on defect location was moderate (kappa, 0.46). Testing time for SWAP was longer than for FDP in both glaucomatous and normal eyes (P<0.001). Short-wavelength automated perimetry and FDP showed similar ability to detect visual dysfunction in patients with preperimetric glaucoma. Long-term follow-up is required to define their role in predicting subsequent SAP defects.

Factors Associated with Variability in Retinal Nerve Fiber Layer Thickness Measurements Obtained by Optical Coherence Tomography

To identify factors associated with variability in retinal nerve fiber layer (RNFL) thickness measurements obtained by optical coherence tomography (OCT). Retrospective observational case series. One hundred fifty consecutive patients with known or suspected glaucomatous optic nerve damage undergoing OCT imaging for RNFL thickness measurement. One eye with known or suspected glaucoma from each patient was scanned twice within the same visit using the Stratus OCT's fast nerve fiber layer thickness acquisition protocol. For each scan, the average RNFL thickness, signal strength (a measure of the amount of light reflecting back from the retina), and analysis confidence (AC, a measure of the quality of the data as reported by the OCT software) were recorded. Retinal nerve fiber layer thickness measurements of the initial and repeat scans for each case were compared, and the difference in thickness measurements was correlated with difference in signal strength, AC (either low or normal), and the average RNFL thickness. Difference in RNFL thickness. The mean difference in RNFL thickness between the initial and repeat scans was 10 microns (12.5%; range, 0.04-86.15 microns). Difference in signal strength between initial and repeat scans positively correlated with the difference in RNFL thickness (Spearman correlation coefficient = 0.44; P<0.001), whereas the average nerve fiber layer thickness negatively correlated with the difference in RNFL thickness (Spearman correlation coefficient = -0.25; P = 0.002). The presence of a scan with low AC was associated with a lower average RNFL thickness and a greater difference in RNFL thickness between the initial and repeat scans. Signal strength variability, low AC, and low RNFL thickness are associated with variability in RNFL thickness measurements obtained by Stratus OCT. Comparability of RNFL thickness measurements between visits may be improved if scans of similar signal strengths without low AC are obtained. This is especially important for patients with moderate glaucomatous optic nerve damage and for patients from whom good quality scans are not obtainable.

Pattern of presentation and outcome of surgical management of primary open angle glaucoma in Kano, Northern Nigeria

Primary open angle glaucoma (POAG) is one of the leading causes of avoidable blindness. Unlike blindness from cataracts, glaucomatous optic nerve damage is irreversible, and prevention of glaucoma is one of the priorities of World Health Organization (WHO) Vision 2020 program. POAG is the commonest type of glaucoma and affects about 33.1 million people worldwide. This study is a five year review of 71 eyes of 63 patients who had trabeculectomy. The study evaluates the pattern of presentation and modality of surgical treatment in our environment. Records of all patients with primary open angle glaucoma operated over a five year period was retrieved. Information extracted included patients bio data, visual acuity, gonioscopic findings, intra ocular pressure as measured with applanation tonometer before and after surgery, and recorded in mmHg. Perimetry was done with 2 m tangent screen and recorded in a perimetry chart. All the patients had trabeculectomy with application of antimetabolite (5-fluorouracil). Extra capsular cataract extraction with or, without posterior chamber intra ocular lens implantation was done on 13 patients. Biometry was not done on patients with cataract. Surgery was done on better eye first in all patients. There were 71 eyes of 63 patients. The male to female ratio was 3:1. The age ranged between 18 to 75 years. 8 patients were below the age of 30 years. One third of the patients were between the ages of 50 to 59 years. At presentation 12 patients (19%) had normal vision (WHO vision category O), 26 patients (41%) were visually impaired, 12 patients (19%) were severely visually impaired and 13 patients (21%) were blind (from co existing cataracts). The cup disc(c: d) ratio assessed before surgery was 0.5 in 9 eyes (13%), 31 eyes (53%) had c: d ratio 0.6 to 0.8 and 18 eyes had c: d ratio of 0.9. All the patients had open anterior chamber angles (Schafer grade 3 and 4). Perimetric changes were; mild peripheral constriction in 5 eyes (8%), peripheral constriction with arcuate scotoma in 19 eyes (26%), constricted fields of 300 or less in 34 eyes (48%), and in 13 eyes there was inability to fixate on target. IOP before surgery was 21 to 30 mm Hg in 12 eyes (17%), and above 31 mm Hg in 69 eyes (83%). Post operative IOP of 10 to 15 mm Hg was obtained in 58 eyes (82%) and 11 eyes (15%) had IOP of 16 to 20 mm Hg. Only 2 eyes (3%) had IOP in the lower twenties. Primary open angle glaucoma is characterized by late presentation. Trabeculectomy with application of 5FU is the surgical treatment of choice in our environment and give good intra ocular pressure control. There is need to increase public awareness on glaucoma to limit this type of avoidable blindness.

Hypoxia/reoxygenation and TGF-β increase αB-crystallin expression in human optic nerve head astrocytes

Reactive astrocytes in glaucomatous optic nerve changes are characterized by an increased expression of αB-crystallin and transforming growth factor-beta (TGF-β). In the pathogenesis of glaucomatous optic nerve damage, ischemia/reperfusion injury may play an important role. The goal of the present study was to determine the influence of hypoxia/reoxygenation and TGF-β on the expression of αB-crystallin in cultured human astrocytes of the optic nerve head (ONH). Cultured human astrocytes were incubated under hypoxic conditions (1% O 2 for 4–12 h) with subsequent reoxygenation (12–24 h). Additionally, cells were treated with 1.0 ng/ml TGF-β1 and TGF-β2 for 12–48 h. Expression of αB-crystallin was examined by Northern- and Western-blotting. Levels of TGF-β1 and TGF-β2 were analyzed by RT-PCR analysis and ELISA. The effect of TGF-β blocking on the hypoxia/reoxygenation modulated expression of αB-crystallin was investigated by simultaneous incubation with neutralizing antibodies against TGF-β during the reoxygenation phase. Hypoxia/reoxygenation increased the expression of αB-crystallin at the mRNA (2.8- to 3.1-fold) and protein level (1.8- to 2.1-fold). Treatment with 1.0 ng/ml TGF-β1 and TGF-β2 for 12–48 h markedly enhanced αB-crystallin mRNA expression approximately three- to fourfold. Using Western blot analysis, this increase ranged from 2 to 3 times. Both cytokines showed a twofold increase after 12 and 24 h of reoxygenation at the mRNA and a two- to threefold increase at the protein level. Simultaneous treatment with neutralizing antibodies against both TGF-β isoforms prevented the hypoxia/reoxygenation-mediated elevation of αB-crystallin. The process of hypoxia/reoxygenation is capable of inducing the expression of αB-crystallin and TGF-ß in cultured ONH astrocytes. Therefore, optimization of conditions leading to hypoxia/reoxygenation in the ONH of glaucomatous patients may help to lower the incidence of characteristic changes in the optic nerve.

Progression of glaucoma associated with the Sirsasana (headstand) yoga posture

This article reports a case of progressive glaucomatous optic neuropathy and visual field loss that occurred in a patient who practiced the Sirsasana (headstand) yoga posture on a daily basis for many years. Visual field analysis was performed through standard automated perimetry. Intraocular pressure (IOP) was measured through pneumotonometry in the sitting position and in the head-down position. Stereo-optic disc photographs were obtained. IOP increased significantly in the head-down position. Optic disc evaluation revealed a new disc hemorrhage in the left eye. Visual field analysis over a period of 2 y showed progression of a superior arcuate defect in the left eye. Transient increases in IOP associated with the yoga headstand posture may lead to progressive glaucomatous optic nerve damage and visual field loss.

Temps-multiplex stéréophotographie : évaluation qualitative et semi-quantitative en 2D et 3D de l’atrophie optique glaucomateuse

Real color documentation of the optic nerve head (ONH) is one of the most important methods in identifying early progression of glaucomatous optic nerve damage. This study qualitatively and semiquantitatively compared the evaluation of ONH photographs, using a 3D time-multiplexing system and conventional 2D photography, visualized on a computer monitor. Twelve 15 degrees sequential stereophotographs from the Erlangen Glaucoma Registry were scanned by a SprintScan 35 Plus Film scanner (Polaroid, Waltham, MA, USA) and converted by computer software (3D-PIX, NuVision, McNaughton Inc., Beaverton, OR, USA) in jps format (3D). The same ONH images were shown in 2D and 3D to 22 subjects: 12 residents and ten ophthalmologists and evaluated using a standardized questionnaire. We observed a significantly better evaluation with stereoscopic pictures for both qualitative parameters (cup depth, visibility of the retinal nerve fibers, and the thinnest location of the neuroretinal rim) and quantitative parameters (c/d ratio and size of the disc, depending on the training level: in 3D better evaluation by the residents, in 2D by the ophthalmologists). With 2D pictures, we found better evaluation of the B zone and the stage of atrophy. Other than the method used for the entire evaluation, there was no significant difference between the groups. For the parameters weighed for clinical importance, the score of correct answers was significantly better with stereoscopic pictures. This study showed a significantly better evaluation of glaucomatous ONH atrophy with 3D images than with 2D pictures, independently of the evaluators' clinical training level. The computer-based evaluation of ONH atrophy using a time-multiplexing system (shutter glasses) may improve the diagnosis of glaucoma patients.

Iris colour, optic disc dimensions, degree and progression of glaucomatous optic nerve damage

To evaluate whether iris colour influences size and shape of the optic nerve head and risk for glaucoma progression. The hospital-based observational study included 1973 eyes of 1012 Caucasian subjects with ocular hypertension or chronic open-angle glaucoma. For all patients, colour stereo optic disc photographs were evaluated, and corneal pachymetry and achromatic perimetry were performed. Main outcome measures were optic nerve head parameters, the development or progression of visual field defects and iris colour. In most of the study groups, size of the optic disc, neuroretinal rim, alpha zone and beta zone of parapapillary atrophy, retinal vessel diameter and central corneal thickness did not differ significantly between eyes with blue, green, brown and mixed iris colour. In the normal-pressure glaucoma group, neuroretinal rim area was smallest in the population with mixed-coloured eyes and largest in the group of eyes with brown irides (P = 0.001 after correction for inter-eye dependency and multiple testing). For the ocular hypertensive subjects and glaucoma patients with follow-up examinations, the rate of development or progression of glaucomatous visual field loss was not significantly associated with iris colour (P = 0.060). In Caucasian subjects, iris colour does not have a major association with the size of the optic nerve head structures, central corneal thickness and retinal arterial diameter. In Caucasian patients with ocular hypertension or chronic open-angle glaucoma, an influence of iris colour on the risk for development or progression of glaucomatous visual field defects could not be confirmed.

Frequency of Optic Disk Hemorrhages in Adult Chinese in Rural and Urban China: The Beijing Eye Study

To determine the frequency of optic disk hemorrhages in the adult Chinese population. Population-based prevalence survey. The study included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40+ years. Mean age was 56.2 +/- 10.6 years. Color optic disk photographs (45 degrees) were morphometrically examined. Optic disk photographs were available for 8655 eyes of 4378/4439 (98.6%) subjects. Prevalence of disk hemorrhages was 107/8655 (1.24%; 95% confidence interval (CI): 1.00%, 1.47%) eyes. Occurrence of disk hemorrhages was significantly associated with glaucomatous optic nerve damage (P < .001; OR: 9.3; 95% CI: 5.6, 15.4) and age (P = .008; 95% CI: 1.01, 1.05). The occurrence of disk hemorrhages was not significantly associated with intraocular pressure (IOP) (P = .63; 95% CI: 0.97, 1.06), refractive error (P = .06; 5% CI: 0.87, 2.18), and visual field score (P = .81; 95% CI: 0.96, 1.03). Defining glaucoma as glaucomatous optic disk appearance, 20/107 (18.7%; 95% CI: 11.2%, 26.2%) disk hemorrhages were found in glaucomatous eyes. Out of 226 glaucomatous eyes, 20/226 (8.8%; 95%CI: 5.12%, 12.58%) eyes showed a disk hemorrhage. Hypertensive glaucoma eyes and normotensive glaucoma eyes did not vary considerably in frequency of disk hemorrhages (P = .44; OR: 1.82; 95% CI: 0.59, 5.68). Disk hemorrhages occur in a frequency of approximately 1.2% in adult Chinese. Major associated factors are glaucomatous optic neuropathy and age. Presence of a disk hemorrhage suggested glaucomatous optic nerve damage with a positive predictive value of approximately 20%. About 9% of glaucomatous eyes showed a disk hemorrhage at the time of examination.

Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma.

BackgroundDBA/2J (D2) mice develop an age-related form of glaucoma. Their eyes progressively develop iris pigment dispersion and iris atrophy followed by increased intraocular pressure (IOP) and glaucomatous optic nerve damage. Mutant alleles of the Gpnmb and Tyrp1 genes are necessary for the iris disease, but it is unknown whether alleles of other D2 gene(s) are necessary for the distinct later stages of disease. We initiated a study of congenic strains to further define the genetic requirements and disease mechanisms of the D2 glaucoma.ResultsTo further understand D2 glaucoma, we created congenic strains of mice on the C57BL/6J (B6) genetic background. B6 double-congenic mice carrying D2-derived Gpnmb and Tyrp1 mutations develop a D2-like iris disease. B6 single-congenics with only the Gpnmb and Tyrp1 mutations develop milder forms of iris disease. Genetic epistasis experiments introducing a B6 tyrosinase mutation into the congenic strains demonstrated that both the single and double-congenic iris diseases are rescued by interruption of melanin synthesis. Importantly, our experiments analyzing mice at ages up to 27 months indicate that the B6 double-congenic mice are much less prone to IOP elevation and glaucoma than are D2 mice.ConclusionAs demonstrated here, the Gpnmb and Tyrp1 iris phenotypes are both individually dependent on tyrosinase function. These results support involvement of abnormal melanosomal events in the diseases caused by each gene. In the context of the inbred D2 mouse strain, the glaucoma phenotype is clearly influenced by more genes than just Gpnmb and Tyrp1. Despite the outward similarity of pigment-dispersing iris disease between D2 and the B6 double-congenic mice, the congenic mice are much less susceptible to developing high IOP and glaucoma. These new congenic strains provide a valuable new resource for further studying the genetic and mechanistic complexity of this form of glaucoma.

Keratometry, Optic Disc Dimensions, and Degree and Progression of Glaucomatous Optic Nerve Damage

To evaluate whether keratometric readings as a measure of corneal shape are associated with optic disc dimensions and with the degree and rate of perimetric progression of chronic open-angle glaucoma or ocular hypertension. The hospital-based observational study included 1826 eyes of 936 patients with ocular hypertension, patients with chronic open-angle glaucoma, or normal individuals. For 733 ocular hypertensive or glaucomatous eyes, follow-up examinations were performed with a mean follow-up time of 58.0+/-34.7 months. Observation procedures were keratometry, morphometric optic disc analysis, tonometry, and perimetry. In the normal study group, area of the neuroretinal rim, alpha zone and beta zone of parapapillary atrophy, and retinal vessel diameter were not significantly associated with keratometric readings. In the entire study population, the optic disc area was significantly (P<0.001; r=-0.27) correlated with low keratometric readings as expressed in diopters. Keratometric readings were significantly (P<0.001 adjusted for age, intraocular pressure, baseline damage, and corneal asphericity) smaller in the normal-pressure glaucoma group than in the normal study group and in the groups with ocular hypertension or primary and secondary open-angle glaucoma. Rate of perimetric progression was not significantly associated with low keratometric readings, either in simple or in multiple Cox regression analysis, controlling for baseline damage, ocular hypertension, age, corneal asphericity, and intraocular pressure. Large optic disc area is statistically significantly, but clinically weakly, correlated with low keratometric readings (diopters). In Caucasian individuals with ocular hypertension and patients with chronic open-angle glaucoma, the rate of development or progression of glaucomatous visual field defects is not significantly associated with keratometric readings.

Three essential elements of glaucomatous optic nerve damage and discrimination of optic nerve rim loss

Three essential elements of glaucomatous optic nerve damages are optic nerve rim loss, retinal nerve fiber layer defects (RNFLD) and optic disc linear hemorrhages. It's suggested that if there are two positive signs detected among the three elements, the diagnosis of the glaucomatous optic nerve damages can be established. There is no definitely described how to identify optic nerve rim loss in the previous textbooks, therefore it is important to know about the morphological features of the physical optic nerve rim and influence factors before discrimination of optic nerve rim loss. Most of physical optic nerve rim are in accordance with ISNT rule, physical large optic cups are also accord with ISNT rule. Exceptional cases exist in two patterns, optic nerve rim loss or normal optic nerve rim morphological variances. The latter includes part of small discs, horizontally oval optic discs, the position of the central retinal vessel trunk and the titled optic discs which affect the morphological feature of optic nerve rim as well. In some small discs, the width of inferior rim is narrower than that of superior rim, therefore, the inferior or the superior rim loss can be evaluated by comparison with nasal rim width. Concerning horizontal oval optic discs, the width of inferior rim and superior rim should be compared to evaluate whether there is the optic nerve rim loss. If those patterns of normal optic nerve rim variances can be recognized, it is not difficult to find the presence of the optic nerve rim loss. However, not all of the optic nerve rim loss is due to glaucomatous optic nerve damages, non-glaucomatous optic nerve damage should be distinguished.

Glaucomatous-Like Cupping Associated with Slow-Growing Supra-Sellar Intracranial Lesions

Purpose: To demonstrate that slow-growing intracranial suprasellar mass lesions can be associated with optic disc cupping, clinically indistinguishable from glaucomatous optic neuropathy. Cases: At a neuro-ophthalmology tertiary clinic, a retrospective chart review identified four patients of presumed normal tension glaucoma and supra-sellar tumors. In all four patients with normal intraocular pressure, the appearance of the optic disc resembled typical glaucomatous optic nerve damage with disc cupping and parapapillary atrophy. Conclusion: In few patients, typical glaucomatous abnormalities of the optic nerve head may occur in association with slow-growing suprasellar tumors.

Validity of Screening for Glaucomatous Optic Nerve Damage Using Confocal Scanning Laser Ophthalmoscopy (Heidelberg Retina Tomograph II) in High-Risk Populations: A Pilot Study

To evaluate whether confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II [HRT II], Heidelberg Engineering, Heidelberg, Germany) is a valid tool for the detection of glaucomatous optic nerve damage. Observational, cross-sectional, nonconsecutive study in Montreal, Canada. Three hundred three nonconsecutive, high-risk persons were enrolled during a 6-month period. Participants underwent HRT II testing and a standard ophthalmologic examination, including gonioscopy, intraocular pressure measurement, and optic disc grading. Positive likelihood ratio (PLR) and negative likelihood ratio (NLR), sensitivities and specificities, positive predictive value (PPV) and negative predictive value (NPV), and kappa coefficients of agreement of Moorfields regression analysis (MRA), cup shape measure (CSM), height variation contour (HVC), and mean retinal nerve fiber layer thickness (MRNFL). Three hundred three participants were enrolled, and 291 were examined clinically; 21 (7.2%) were found to have glaucoma. Heidelberg Retina Tomograph II testing was performed successfully and was of acceptable quality in 531 of 601 eyes (88%). When MRA was compared with the clinically based diagnosis, the weighted kappa coefficient was kappa = 0.567 (95% confidence interval [CI], 0.42-0.71) for the right eye and kappa = 0.516 (95% CI, 0.37-0.66) for the left eye. Best kappa coefficient of agreement was seen when normals were grouped with suspects in both clinical and MRA diagnosis (kappa = 0.604; 95% CI, 0.409-0.799 in the right eye). Depending on the gold standard and test-positive definitions for glaucoma, specificity ranged from 87% to 97%, sensitivity from 25% to 100%, PPV from 28% to 68%, NPV from 84% to 100%, PLR from 5.0 to 19.2, and NLR from 1.3 to 6.2. When CSM, HVC, and MRNFLT were compared with clinical diagnosis, all outcome measures were found to have lower ranges: specificity from 46.9% to 83.7%, sensitivity from 36.5% to 76.9%, PPV from 6% to 36%, NPV from 80% to 99%, PLR from 0.8 to 4.0, NLR from 0.9 to 3.0. The results of this study suggest that a glaucoma screening program may be effective in detecting glaucoma when targeting high-risk populations. Heidelberg Retina Tomograph II testing may prove to be a useful tool in detecting glaucomatous optic nerve damage and could be used as part of a complete glaucoma screening protocol.

Glaukomrisiko und Hornhautdicke

Intraocular pressure is still the most important risk factor for the development of glaucomatous optic nerve damage. There is growing evidence that corneal thickness is a risk factor for the development of glaucoma. This might be caused by the effect of corneal thickness on intraocular pressure (IOP) measurements. Goldmann applanation tonometry measurements are correlated with corneal thickness. Thick corneas lead to false high readings whereas thin corneas lead to false low readings. If corneal thickness as a risk factor for glaucoma is only related to the dependency of IOP measurements on corneal thickness or is related to possible different biomechanical tissue properties in glaucomatous eyes is not known. However, a large proportion of the corneal thickness effect seems to be related to the effect on IOP readings by applanation tonometry. Neglecting corneal thickness can lead to false measurements of IOP with consequent misdiagnosis and false treatment. Therefore, measurements of corneal thickness should be performed in glaucoma patients and suspects.

Predictive Factors for Progressive Optic Nerve Damage in Various Types of Chronic Open-angle Glaucoma

To evaluate whether various types of chronic open-angle glaucoma differ in predictive factors for progression of glaucomatous optic nerve damage. Observational cohort study. Prospective observational clinical study. 517 eyes of 300 Caucasian patients with chronic open-angle glaucoma with elevated intraocular pressure (primary open-angle glaucoma, n = 289; secondary open-angle glaucoma, n = 50) and with normal intraocular pressure (n = 178). During follow-up (median: 49 months, 6 months-130 months), all patients underwent repeated evaluation of color stereo optic disk photographs and white-on-white visual field examination. Progression of glaucoma was defined as neuroretinal rim loss during the study period. For patients with elevated intraocular pressure, significantly predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim, and larger area of beta zone of parapapillary atrophy. In contrast, in the normal intraocular pressure group, a significant predictive factor was presence of disk hemorrhages at baseline. Within the patients with elevated intraocular pressure, the primary open-angle glaucoma group and the secondary open-angle glaucoma group did not differ in predictive factors for progression of glaucoma. Open-angle glaucoma patients with normal intraocular pressure and open-angle glaucoma patients with elevated intraocular pressure differ in predictive factors for eventual progression of glaucomatous optic nerve damage. It may have clinical importance and may be helpful in the discussion of the pathogenesis of the glaucomas.

Central Corneal Thickness Correlated with Glaucoma Damage and Rate of Progression

To evaluate whether the amount of glaucomatous optic nerve damage at presentation of the patient and the rate of progression of glaucoma during follow-up are related to central corneal thickness. The prospective observational clinical study included 861 eyes of 454 white subjects (239 normal eyes of 121 subjects, 250 ocular hypertensive eyes of 118 patients, 372 eyes of 215 patients with chronic open-angle glaucoma). For 567 eyes (304 patients) with ocular hypertension or chronic open-angle glaucoma, follow-up examinations were performed, with a mean follow-up time of 62.7 +/- 33.2 months (median, 60.8; range, 6.2-124.9). All patients underwent qualitative and morphometric evaluation of color stereo optic disc photographs and white-on-white visual field examination. Central corneal thickness was measured by corneal pachymetry. Central corneal thickness correlated significantly (P < 0.001) and positively with the area of the neuroretinal rim and negatively with the loss of visual field. Development or progression of glaucomatous visual field defects detected in 119 (21.0%) eyes was statistically independent of central corneal thickness, in univariate (P = 0.99) and multivariate Cox regression analyses (P = 0.19). At the time of patient referral, the amount of glaucomatous optic nerve damage correlated significantly with a thin central cornea. Progression of glaucomatous optic nerve neuropathy was independent of central corneal thickness, suggesting that central corneal thickness may not play a major role in the pathogenesis of progressive glaucomatous optic nerve damage.

Central Corneal Thickness and Thickness of the Lamina Cribrosa in Human Eyes

Since central corneal thickness may inversely influence the amount and rate of progression of glaucomatous optic nerve damage and because lamina cribrosa thickness may be of importance in susceptibility to glaucoma, it was the purpose of the present study to evaluate whether central corneal thickness is related to lamina cribrosa thickness. The histomorphometric study included 111 enucleated nonglaucomatous eyes of 111 white subjects. On anterior-posterior histologic sections through the pupil and the central optic disc region, the thickness of the cornea, lamina cribrosa, and peripapillary sclera and the shortest distance between the intraocular space and the cerebrospinal fluid space were measured. Axial length ranged between 20 and 32 mm. Mean central corneal thickness (mean +/- SD: 616.6 +/- 108.3 microm) and mean central lamina cribrosa thickness (378.1 +/- 117.8 microm) were statistically independent of each other (P = 0.15; correlation coefficient, r = 0.14). In a similar manner, lamina cribrosa thickness at the optic disc border was statistically independent of central corneal thickness (P = 0.51; r = 0.06) and peripheral corneal thickness (P = 0.34; r = 0.09). In a parallel way, peripapillary scleral thickness (P = 0.84) and the shortest distance between the prelaminar space and cerebrospinal fluid space (P = 0.10) were statistically independent of central corneal thickness. In nonglaucomatous human globes, central corneal thickness may not correlate significantly with lamina cribrosa thickness, peripapillary scleral thickness, and shortest distance between intraocular space and cerebrospinal fluid space. Histologic artifact and sectioning methods could partially account for the lack of an association. The study results may suggest clinically that an assumed relationship between central corneal thickness and susceptibility to glaucoma cannot be explained by an anatomic correspondence between corneal thickness and histomorphometry of the optic nerve head.

Clinical implications of peripapillary atrophy in glaucoma

To elucidate peripapillary atrophy in glaucomatous optic neuropathy; its ranking in the morphologic diagnosis of the glaucoma, and its value for the differentiation of various types of chronic open-angle glaucoma, for the separation of glaucomatous eyes from nonglaucomatous eyes, and for the detection of progression of glaucoma. Recent studies showed an association of peripapillary atrophy with glaucoma and the eventual development of glaucomatous disc hemorrhages independent of a small neuroretinal rim area, and an association between increasing peripapillary atrophy and progressive glaucoma. A ranking of optic disc parameters to detect glaucomatous damage revealed that the alpha and beta zones of peripapillary atrophy, compared with neuroretinal rim parameters, are less useful. Pseudoexfoliation syndrome without glaucoma is not a risk factor for peripapillary atrophy. In arteritic anterior ischemic optic neuropathy, peripapillary atrophy does not enlarge. Peripapillary atrophy does not differ markedly between Europeans and South Indians. In contrast to the position of the central retinal vessel trunk, the presence and position of cilioretinal arteries do not markedly influence the progression of peripapillary atrophy in glaucoma. Peripapillary chorioretinal atrophy is one among several morphologic variables to detect glaucomatous abnormalities. Ranking optic disc variables for the detection of glaucomatous optic nerve damage, peripapillary atrophy is a variable of second order. It is useful for the differentiation of various types of chronic open-angle glaucomas. In contrast to glaucomatous eyes, eyes with nonglaucomatous optic nerve atrophy, including eyes after arteritic anterior ischemic optic neuropathy, do not show an enlarged peripapillary atrophy.

Age related optic nerve axonal loss in adult Brown Norway rats

The effect of age on the number and morphology of optic nerve axons in adult Brown Norway rats (5–31 months old) ( n=29) was examined using transmission electron microscopy (TEM). By manually counting every axon in areas representing 60% of the optic nerve cross-section, we found a significant negative correlation between age and axon count ( R 2=0·18, P<0·05). However, when the oldest animals were omitted, the relationship was no longer statistically significant. Simultaneously, the proportion of spontaneously degenerating axons increased at an exponential rate ( R 2=0·79, P<0·05), with significantly more degeneration in the 31-month group than in 5-month-old animals (ANOVA, P<0·05). This study demonstrates, using quantitative TEM methods, that optic nerve axonal numbers are relatively constant throughout the majority of the adult life of the Brown Norway rat, an increasingly popular strain for glaucoma research. Total axonal loss with aging is substantially less than that reported for other strains. The reduction in axonal numbers and the rate of axonal degeneration do not appear significantly altered until the last few months of life, failing to support some studies that have concluded that optic nerve axon loss in adult rats is linear. However, they do agree with other studies in the rat, and a similar study performed in non-human primate eyes, that concluded that aging changes in the optic nerve and retina follow a complex pattern. Therefore, the impact of animal age must be considered when modeling the course and pathophysiology of experimental glaucomatous optic nerve damage in rats.