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.     

New technologies for diagnosing and monitoring glaucomatous optic neuropathy.

BACKGROUND: Recently, instruments have been developed to provide real-time, quantitative measurements of the optic disc and retinal nerve fiber layer (RNFL) for use in glaucoma management. Our objective is to (1) provide an overview of two of these instruments, the confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT) and scanning laser polarimeter (Nerve Fiber Analyzer, NFA) and (2) compare measurements obtained with these instruments to clinical features used in the diagnosis of glaucoma. METHODS: Twenty glaucoma patients, 4 normal subjects and 20 glaucoma subjects were included. All subjects had images obtained with the HRT and NFA, and RNFL and optic disc photography completed within 5 weeks of each other. The HRT results were compared with qualitative evaluation of stereophotographs of the optic disc, and NFA results were compared against a semi-quantitative RNFL photograph severity score. RESULTS: Twenty-five (57%) subjects had thinning of the neuroretinal rim identified by evaluation of stereoscopic optic disc photographs. Despite overlap, HRT measurements of rim volume, rim area, and rim/disc ratio were significantly smaller in eyes with evidence of rim thinning than in eyes with no evidence of rim thinning. Moderate to severe RNFL damage was detected by evaluation of photographs in 25 (57%) of subjects. NFA RNFL thickness measures were smaller in eyes with moderate to severe RNFL damage than in relatively healthy eyes. CONCLUSIONS: Previous studies have documented the reproducibility of these instruments and suggested analytic techniques for improving their ability to differentiate between normal and glaucoma eyes. Our results indicate that despite overlap in values, these instruments provide measurements that reflect clinically relevant features of the optic disc and RNFL. Whether these technologies can improve our ability to detect glaucomatous progression over time needs to be determined with well-designed longitudinal studies and comparison with established diagnostic techniques for evaluating glaucomatous optic neuropathy.     

Study of the optic papilla and nerve fiber layer in glaucoma]

BACKGROUND: For diagnosis and follow-up of glaucoma an exact evaluation of the optic nerve disc and the nerve fiber layer is necessary. METHODS: The slit-lamp evaluation of the optic nerve disc and nerve fiber layer is presented as well as the evaluation with the Nerve Fiber Analyzer and the Heidelberg Retina Tomograph. RESULTS: Signs of a glaucomatous optic disc include a difference of more than 0.2 in the vertical cup to disc (CD) ratio between the eyes, a vertical CD ratio exceeding more than 0.1 the horizontal, larger CD ratios in small optic discs, notching of the neuroretinal rim, an enlarged zone beta of parapapillary chorioretinal atrophy, and peripapillary hemorrhages. Atrophy of the nerve fiber layer may be localized or diffuse. Both types of atrophy may be present at the same time. CONCLUSIONS: Knowledge of all signs of the glaucomatous optic disc and forms of nerve fiber layer atrophy allows an earlier diagnosis of glaucoma and an earlier recognition of progression.     

Glaucomatous optic nerve atrophy in small discs with low cup-to-disc ratios

Glaucomatous optic nerve damage has generally been associated with high cup-to-disc ratios. Fifteen eyes of nine patients with increased intraocular pressure and glaucomatous visual field loss but low cup-to-disc ratios are reported. The optic disc area was significantly (P less than 0.01) smaller than in 429 normal subjects and 556 glaucoma patients with high cup-to-disc ratios. Parapapillary chorioretinal atrophy was significantly larger and retinal nerve fiber bundles were significantly less visible than in the normal group. The latter two parameters were not significantly different in the glaucoma groups with low and high cup-to-disc ratios when the groups were matched for mean perimetric loss. The authors conclude that in eyes with small optic discs, glaucomatous optic nerve damage may be indicated more sensitively by parapapillary changes than by cup-to-disc ratios. Glaucomatous eyes with small optic nerve heads can have misleadingly low cup-to-disc ratios.     

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.     

Early detection of glaucoma damage with the Optic Nerve Head Analyzer. A case report

We present a first case report demonstrating that the Optic Nerve Head Analyzer offers a potential chance to establish glaucomatous damage of the optic disc prior to the appearance of clinically detectable visual field defects. Computerized analysis of the optic disc of a female patient with unilateral irido-corneo-endothelial syndrome revealed a marked loss of neuroretinal rim within sixteen month of follow-up on the affected eye. The neuroretinal rim of her healthy eye was unchanged during this period. Identification and documentation of this ongoing disc damage by means of conventional techniques such as disc photography or nerve fiber layer photography were much more uncertain. Up to now no visual field loss was detectable by computerized perimetry (Octopus G1). This clinical case supports our previous conclusion from theoretical studies: For early diagnosis of glaucoma by means of computerized disc analysis with the Optic Nerve Head Analyzer follow-up measurements of the disc structure are more valid than single examinations.     

Expert agreement in evaluating the optic disc for glaucoma.

The authors studied intraobserver and interobserver agreement, under monoscopic and stereoscopic conditions, in estimating vertical cup-to-disc ratios and in assessing whether a disc had glaucomatous damage. Six glaucoma experts evaluated 75 optic disc photographs under both viewing conditions. The experts also re-evaluated 25 photographs. Intraobserver agreement in estimating vertical cup-to disc ratios was high (median weighted kappa, 0.79). Interobserver agreement in estimating vertical cup-to-disc ratios was moderate (stereoscopic median weighted kappa, 0.67); individual experts differed by as much as 0.2 disc diameters (DD) monoscopically and 0.16 DD stereoscopically. The observers estimated larger vertical cup-to-disc ratios when evaluating the same discs under stereoscopic conditions than under monoscopic conditions. Intraobserver agreement in assessing glaucomatous disc damage was substantial (median kappa, 0.76). Interobserver agreement in assessing glaucomatous damage was moderate (stereoscopic median kappa, 0.50). This study confirms the ability of experts to reliably evaluate the optic disc within themselves and emphasizes the need for developing standardized methods for interobserver evaluation of the optic disc in glaucoma.     

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.     

Intraocular pressure-dependent dynamic changes of optic disc cupping in adult glaucoma patients.

The authors performed a study of intraocular pressure-dependent changes in optic disc cupping in 17 adults with chronic open-angle glaucoma. Analyses with the Rodenstock Optic Nerve Head Analyzer were performed at baseline low intraocular pressure during therapy, after elevation of intraocular pressure (from therapeutic failure or noncompliance), and after reduction of intraocular pressure with successful therapy. Optic disc cupping increased significantly upon short-term increase of intraocular pressure from baseline of 20.4 +/- 2.5 mmHg to 31.1 +/- 5.9 mmHg. Optic disc cupping reverted to baseline after persistent intraocular pressure reduction to 19.3 +/- 4.8 mmHg. These data demonstrate intraocular pressure-dependent dynamic changes of optic disc cupping in patients with demonstrable glaucomatous optic nerve damage. They underscore the detrimental effect of elevated intraocular pressure and the beneficial effect of intraocular pressure reduction on optic disc cup changes.     

Retinal nerve fiber layer measurements using laser scanning polarimetry in different stages of glaucomatous optic nerve damage

PURPOSE: To evaluate the diagnostic value of polarimetric measurements of the retinal nerve fiber layer (RNFL) thickness in different stages of glaucomatous optic nerve damage. METHODS: The study included 92 eyes of 46 controls (age 41.0+/-13.7 years) and a heterogeneous group of 232 eyes of 135 patients with different stages of glaucomatous optic nerve damage (age 54.0+/-10.2 years; 68 patients with primary open-angle glaucoma, 56 with normal-pressure glaucoma and 11 patients with secondary glaucoma due to primary dispersion syndrome or pseudoexfoliation syndrome). All control subjects and patients underwent complete ophthalmological examinations including scanning laser polarimetry of the RNFL using the GDx (Laser Diagnostic Technologies, San Diego, Calif.) and 15 degrees color stereo optic disc photographs. Only subjects and patients with disc area less than 3.4 mm(2) were included in the study. The total glaucoma group were divided into four subgroups according to the morphological criteria of the neuroretinal rim. RESULTS: The stage of morphological glaucomatous optic nerve damage was classified as follows: stage 0: n=92, stage 1: n=103, stage 2: n=65, stage 3: n=40, and stage 4: n=19. Differences in mean polarimetric retardation between controls and eyes with glaucoma were significant for all parameters except the variable symmetry. The most significant differences between controls and eyes with glaucomatous optic nerve damage were found with the "number" variable assigned by the neural network analysis ( P<0.001). With increasing stage of glaucomatous optic nerve damage, separation of the variable "the number" increased significantly. At a predetermined specificity of 90% the sensitivity of the groups with different stages of morphological glaucomatous optic nerve damage increased from 32% for stage 1 to 90% for stage 4. CONCLUSION: Polarimetric measurement of the RNFL thickness is significantly associated with morphological glaucomatous optic nerve damage. The fast performance, easy handling, and low cost of RNFL polarimetry mean that it can be included in the routine examination of glaucoma patients. Further study and refinement of this technique are indicated to improve its usefulness in both clinical diagnosis and in population-based case identification.     

Humphrey visual field and frequency doubling perimetry in the diagnosis of early glaucoma

PURPOSE: To compare Humphrey Visual Field Analyzer (HVF) and Frequency Doubling Perimetry (FDP) testing in the diagnosis of early glaucoma. METHODS: We performed HVF (24-2 standard full threshold) and FDP (N-30) evaluations in 34 consecutive patients with early primary glaucoma and 96 normal subjects. Early glaucoma was defined on the basis of disc changes of glaucoma; the mean deviation on white-on-white perimetry had to be no worse than 6 decibels. Glaucomatous optic neuropathy was defined as a combination of cup-disc asymmetry of more than 0.2, notching, excavation, thinning or pallor of superior or inferior neuroretinal rims, retinal nerve fibre layer defects of the wedge or diffuse type and neuroretinal rim haemorrhage. Both the glaucoma patients and normal subjects had vision better than 6/9 with correction. They had no media opacities other than early nuclear sclerosis and no fundus pathology. Further, normal subjects were free of systemic diseases known to affect the retina or optic nerve. The sensitivity and specificity of HVF and FDP were calculated. RESULTS: There were 44 eligible eyes among the 34 subjects. The glaucomatous disc findings included notch (n=8), pallor (n=21), thinning (n=23) and haemorrhage (n=1) of the neuroretinal rim. The sensitivity and the specificity of the HVF were 52.3% and 57.3% respectively. The sensitivity and the specificity of FDP were 65.9% and 61.5% respectively. CONCLUSION: The difference between FDP and HVF in the diagnosis of early glaucoma is not marked.     

Non-quantitative morphologic features in normal and glaucomatous optic discs

Glaucoma is associated with changes of the optic disc topography. Using color stereo photographs we examined non-quantitative signs in 584 optic discs of 308 patients with chronic primary open-angle glaucoma and in 383 optic discs of 236 age and refraction matched normal subjects. Only one eye per patient and normal subject was chosen for statistical analysis. Highest predictive value to differentiate between normal and glaucoma eyes had the parameters 'changes in the juxtapapillary retinal nerve fiber layers' (86.7%), 'abnormal size (79.8%) and abnormal location (68.6%) of the parapapillary chorio-retinal atrophy', 'smallest neuroretinal rim part outside of the temporal horizontal disc sector' (78.5%), and area with cupping larger than area with pallor' (68.2%). Characteristics with high specificity and low sensitivity were 'optic disc haemorrhages', 'bared cilioretinal arteries', and 'bared circumlinear vessels'. With their evaluation being independent of sophisticated techniques the non-quantitative parameters are helpful for the ad hoc diagnosis of glaucomatous optic nerve damage.     

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。     

Nerve fiber layer and optic disc fluorescein defects in glaucoma and ocular hypertension

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.     

Detection of nerve fiber bundle defects with laser polarimetry in glaucoma: a clinical study with the Nerve Fiber Analyzer I

PURPOSE: To verify whether nerve fiber bundle defects (NFBD) can be detected by the polarization technique of the Nerve Fiber Analyzer I (NFA I), we compared the localization of localized visual field (VF) defects with the localization of the expected corresponding NFBD. METHODS: We examined 25 eyes of 25 glaucoma patients. All examined glaucomatous eyes had localized VF defects stage II and III. The glaucoma stage was defined by examination of the central 30 degrees VF using computer perimetry. NFBD were determined by masked examination of NFA I images by three examiners. As controls 22 eyes of 22 normals were examined. RESULTS: In 18 (72%) of 25 glaucomatous eyes the three examiners agreed in their findings. In 15 of 25 glaucomatous eyes (60%) all three examiners found a NFBD, which corresponded to a localized VF defect. In 18 of 22 healthy eyes all three examiners found no NFBD. The first examiner had no false-positive results, the second three, and the third four. CONCLUSIONS: The three examiners often disagreed in their findings of NFBD, which indicates high subjective variability. Examiner-dependent specificity and sensitivity show that detection of glaucomatous NFBD is often not possible by laser polarimetry (software version 06/93).     

Discriminant analysis models for early detection of glaucomatous optic disc changes

AIM: To evaluate and compare four different mathematical formulas for the early detection of morphometric optic nerve head changes in chronic open angle glaucoma. METHODS: The optic nerve heads of 161 patients with perimetrically defined glaucomatous optic nerve damage and of 194 normal subjects were examined by confocal laser scanning tomography. Using four formulas of linear discriminant analysis and the optic cup shape measure as the single optic disc variable, the predictive power of each of these methods was examined to differentiate between the normal eyes and the glaucoma eyes. RESULTS: The highest predictive power had an optic disc sector based formula, in particular in eyes with medium and large optic discs. This optic disc sector based formula was the one with the best agreement with the other formulas examined. It achieved a better predictability than any single optic disc variable evaluated. CONCLUSIONS: Combining quantitative optic disc variables by discriminant analysis functions, the predictive power of semiautomatic quantitative optic nerve head evaluation can be improved by providing the ophthalmologist with a diagnostic score for the detection of glaucomatous optic nerve damage. Because of the pattern of glaucomatous neuroretinal rim loss, an optic disc sector based discriminant formula may have a higher diagnostic precision than other formulas in detecting early glaucomatous damage.     

Identifying early glaucomatous changes. Comparison between expert clinical assessment of optic disc photographs and confocal scanning ophthalmoscopy

OBJECTIVE: To compare the ability of expert clinicians, using qualitative assessment of stereoscopic optic disc photographs, and confocal scanning laser ophthalmoscope imaging to discriminate between healthy persons and patients with early glaucoma. DESIGN: Comparative instrument validation study. PARTICIPANTS: Seventy-two healthy persons and 51 patients with early glaucoma (average visual field mean deviation, -3.6 dB). Early glaucoma was defined as a history of ocular hypertension and a reproducible visual field defect scoring 5 or less in the Advanced Glaucoma Intervention Study classification, regardless of optic disc appearance. INTERVENTION: Stereoscopic optic nerve head (ONH) photography and Heidelberg Retina Tomograph (HRT) imaging, (Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES: Ability of clinical assessment of stereoscopic ONH photographs and analysis of HRT parameters, taking into account the optic disc size, to detect early glaucomatous optic disc changes. RESULTS: The specificity of the majority opinion of five observers to detect early glaucomatous optic disc changes was 94.4%, with a sensitivity of 70.6%. Using the HRT analysis, the specificity was 95.8% and the sensitivity was 84. 3%. CONCLUSIONS: Heidelberg Retina Tomograph image analysis that takes into account the optic disc size is more sensitive than clinical assessment of stereoscopic optic disc photographs in distinguishing between healthy persons and patients with early glaucoma.     

The influence of age, sex, race, refractive error and optic disc parameters on the sensitivity and specificity of scanning laser polarimetry

PURPOSE: To evaluate the influence of age, sex, race, refractive error and optic disc topography on the sensitivity and specificity of scanning laser polarimetry (SLP) in the diagnosis of glaucoma. METHODS: A total of 88 normal individuals and 95 glaucoma patients were included in this study. Glaucoma was defined on the basis of both optic nerve damage and visual field defects. Scanning laser polarimetry, optic disc topography, automated perimetry and refractometry were performed in all subjects. The sensitivity and specificity of SLP were assessed applying a previously calculated cut-off to a previously described linear discriminant function (LDF). RESULTS: The sensitivity and specificity of SLP in the study population were 82% and 83%, respectively. Sensitivity and specificity were not affected by age, sex, race, average disc diameter or disc area. The sensitivity of SLP tended to be higher in myopes (93%) than in emmetropes (80%) and hyperopes (71%) (p = 0.08). Sensitivities were higher in individuals with cup areas > 0.96 mm(2) (89%), rim areas < or = 1.36 mm(2) (92%), and cup area/disc area ratios > 0.45 (89%) (p < 0.05). Stepwise logistic regression analysis indicated that the presence of a cup area > 0.96 mm(2) and a rim area < 1.36 mm(2) significantly increased the sensitivity of the LDF, whereas a cup area/disc area ratio < or = 0.45 significantly increased the specificity of the LDF. CONCLUSION: The sensitivity and specificity of SLP may be influenced by refractive error and optic disc parameters that are affected by glaucomatous damage (cup area, rim area and cup area/disc area ratio). These parameters must be considered in studies evaluating the sensitivity and specificity of optic nerve/retinal nerve fibre layer imaging technologies.