Central retinal vessel trunk exit and location of glaucomatous parapapillary atrophy in glaucoma.

OBJECTIVE: To evaluate whether the position of the central retinal vessel trunk exit on the lamina cribrosa spatially correlates with the location of parapapillary atrophy in glaucoma. DESIGN: Clinic-based, observational, cross-sectional study. PATIENTS: Color stereo optic disc photographs of 95 patients with primary or secondary open-angle glaucoma and 65 healthy persons were morphometrically evaluated. The intrapapillary and parapapillary region was divided into four quadrants. We determined the position of the central retinal vessel trunk exit on the lamina cribrosa surface and measured the area of parapapillary atrophy and neuroretinal rim in the four quadrants. MAIN OUTCOME MEASURES: The area of neuroretinal rim and parapapillary atrophy and the position of the central retinal vessel trunk exit. RESULTS: Comparing measurements between opposite disc quadrants showed that beta zone of parapapillary atrophy was significantly (P < 0.05) larger and that the neuroretinal rim was significantly smaller when beta zone and neuroretinal rim were measured in the disc quadrant most distant to the central retinal vessel trunk exit, than if the beta zone and neuroretinal rim were measured in the quadrant containing the vessel trunk exit. Comparing measurements in the disc quadrants between eyes with different positions of the central retinal vessel trunk exit revealed that, in the respective disc quadrant, the beta zone was significantly larger and the neuroretinal rim was smaller in eyes with the vessel trunk exiting in the opposite disc quadrant than in eyes with the vessel trunk exit located in the respective disc quadrant where the measurements were obtained. CONCLUSIONS: Position of the central retinal vessel trunk exit on the lamina cribrosa influences the location of parapapillary atrophy in glaucoma. The longer the distance to the central retinal vessel trunk exit, the more enlarged is parapapillary atrophy and the smaller is the neuroretinal rim. This relationship agrees with the spatial relationship between glaucomatous neuroretinal rim loss and enlarged parapapillary atrophy in glaucoma. Diagnostically, it may indicate that, in eyes with an abnormal configuration of parapapillary atrophy or with an abnormal position of the central retinal vessel trunk exit, early glaucomatous rim changes should be looked for in the disc sector that is most distant to the central retinal vessel trunk exit and where parapapillary atrophy may be relatively large.

Influence of optic disc size on neuroretinal rim shape in healthy eyes.

PURPOSE: To evaluate the influence of optic disc size on segmental neuroretinal rim area in healthy eyes. PATIENTS AND METHODS: The study included 193 eyes of 193 healthy patients with physiologic disc cupping. On 15 degrees color stereophotographic optic disc diapositives, optic disc area and neuroretinal rim area were morphometrically determined in 36 radial optic disc segments each measuring 10 degrees. RESULTS: The correlations of segmental rim area to disc area were significantly strongest (P < 0.01) and the regression lines were steepest in the inferior disc region, and the values were lowest in the temporal disc region. Complementary to the rim data, the correlations of segmental cup area to disc area were significantly strongest (P < 0.01) and the regression lines were steepest in the temporal disc region, and the values were lowest in the inferior disc region. In comparison with neuroretinal rim area, cup area was significantly (P < 0.01) more strongly correlated with disc area and the regression line was steeper in the whole optic disc and in each disc segment. The regional distribution of the widest rim part and smallest rim part was independent of disc size. CONCLUSIONS: The increase of rim area and cup area with increasing disc size differs between various disc regions. Because cup area increases more than rim area with increasing disc size, correction for disc size may be more important for segmental cup area than for segmental rim area. The rim shape with respect to the location of the smallest or broadest rim part is independent of disc size.

[Exit of the retinal central vascular trunk and extent of para-papillary atrophy]. / Austritt des retinalen Zentralgefässstammes und Ausprägung der parapapillären Atrophie.

PURPOSE: To evaluate whether the position of the central retinal vessel trunk exit on the lamina cribrosa spatially correlates with the location of parapapillary atrophy in glaucoma. METHODS: Color stereo optic disc photographs of 79 patients with primary or secondary open-angle glaucoma and 53 normal subjects were morphometrically evaluated. We determined the position of the central retinal vessel trunk exit on the lamina cribrosa surface and measured the area of parapapillary atrophy in four 90 degrees quadrants. RESULTS: After correction for normal values, the beta zone area of parapapillary atrophy in the glaucoma eyes was significantly larger, when measured in the disc quadrant most distant to the central retinal vessel trunk exit than as if measured in the quadrant containing the vessel trunk exit. CONCLUSIONS: Position of the central retinal vessel trunk exit on the lamina cribrosa influences the location of parapapillary atrophy in glaucoma. The longer the distance to the central retinal vessel trunk exit, the more enlarged is parapapillary atrophy.

Comparison of measurements of neuroretinal rim area between confocal laser scanning tomography and planimetry of photographs.

BACKGROUND: To compare neuroretinal rim area measurements by confocal scanning laser tomography and planimetric evaluation of optic disc photographs. METHODS: For 221 patients with primary and secondary open angle glaucoma, 72 subjects with ocular hypertension, and 139 normal subjects, the optic disc was morphometrically analysed by the confocal scanning laser tomograph HRT (Heidelberg retina tomograph) and by planimetric evaluation of stereo colour optic disc photographs. RESULTS: Absolute rim area and rim to disc area were significantly (p < 0.0001) larger with the HRT than with planimetric evaluation of photographs. Differences between the two methods were significantly (p < 0.01) larger in normal eyes with small cupping than in normal eyes with large cupping, and differences were significantly (p < 0.01) larger in glaucomatous eyes with marked nerve damage than in glaucomatous eyes with moderate nerve damage. Coefficients of correlations between rim measurements of both methods were R2 = 0.60 for rim to disc area and R2 = 0.33 for absolute rim area. Planimetric measurements of rim area correlated significantly (p < 0.05) better than HRT determinations of rim area with mean visual field defect and retinal nerve fibre layer visibility. CONCLUSIONS: Measurements of absolute rim area and rim to disc area are significantly larger with the HRT compared with planimetry of disc photographs. Differences between both methods depend on disc area, cup size and glaucoma stage. The reason may be that the HRT measures the retinal vessel trunk as part of the neuroretinal rim. The differences between both methods, which should be taken into account if disc measurements performed by both methods are compared with each other, may not influence the main advantage of the HRT--that is, morphological follow up examination of patients with glaucoma.

Prevalence of diabetes mellitus and arterial hypertension in primary and secondary open-angle glaucomas.

BACKGROUND: This study was carried out to evaluate the prevalence of diabetes mellitus and arterial hypertension in the open-angle glaucomas. METHODS: The study consisted of 529 patients with primary open-angle glaucoma, including 170 patients with the age-related atrophic type and 22 patients with the highly myopic type; 152 patients with secondary open-angle glaucoma, including 85 patients with pseudoexfoliative glaucoma; 56 patients with the focal type of normal-pressure glaucoma; and 660 nonglaucomatous subjects in the control group. For all study groups, age-matched control groups were formed. RESULTS: Prevalence of diabetes mellitus and arterial hypertension did not vary significantly (P > 0.25; chi-square test) between the non-highly myopic primary open-angle glaucoma groups and the control groups. In highly myopic primary open-angle glaucoma, pseudoexfoliative glaucoma, and focal normal-pressure glaucoma, diabetes mellitus and arterial hypertension were less common; however, not in all cases was the difference from the control group significant. CONCLUSIONS: The results suggest that diabetes mellitus and arterial hypertension are not more common in patients with primary and secondary open-angle glaucomas than in age-matched nonglaucomatous subjects. In agreement with some previous epidemiologic studies, diabetes mellitus and arterial hypertension may not be positively associated with the primary or secondary open-angle glaucomas.

Pressure-dependent neuroretinal rim loss in normal-pressure glaucoma.

PURPOSE: To evaluate whether, in normal-pressure glaucoma, the level of intraocular pressure is correlated with the degree of glaucomatous optic nerve damage. METHODS: Color stereo optic disk photographs of 98 eyes with the focal type of normal-pressure glaucoma, 17 eyes with the highly myopic type of normal-pressure glaucoma, and 36 eyes with the age-related atrophic type of primary open-angle glaucoma were morphometrically evaluated. RESULTS: In all three study groups, neuroretinal rim area declined significantly (P < .05) with increasing maximal intraocular pressure values. CONCLUSIONS: In different forms of open-angle glaucoma with normal intraocular pressure, eyes with relatively high intraocular pressure have more pronounced optic nerve damage than do eyes with relatively low intraocular pressure. This suggests a barotraumatic aspect in the pathogenesis of optic nerve damage in the normal-pressure glaucomas. It implies that therapeutically, an intraocular pressure in the low-normal range may less likely be associated with glaucoma damage than an intraocular pressure in the upper-normal range would be.

Optic disc shape, corneal astigmatism, and amblyopia.

OBJECTIVE: The cornea and the optic disc form the anteroposterior opening of the sclera. This study evaluated whether an abnormal shape of the optic disc is associated with an abnormal configuration of the cornea measured as corneal astigmatism. DESIGN: The study design was a cross-sectional one. PARTICIPANTS: The study included 882 subjects (430 women, 452 men) with a mean age of 45.9 +/- 13.6 years (mean +/- standard deviation; range, 8-87 years) and a mean refractive error of -1.09 +/- 2.76 diopters (range, -21.0 diopters to +7.0 diopters). INTERVENTION: Corneal astigmatism was determined by keratometry, and the optic disc was analyzed morphometrically by planimetric evaluation of optic disc photographs. MAIN OUTCOME MEASURES: Corneal astigmatism, ratio of minimal-to-maximal disc diameter, and optic disc form factor were measured. RESULTS: The amount of corneal astigmatism was significantly (P < 0.001) correlated with an increasingly elongated optic disc shape. Corneal astigmatism was significantly (P < 0.01) higher in eyes with tilted discs. It was significantly (P = 0.006) smaller in eyes with an almost circular disc shape. Amblyopia was significantly (P < 0.05) associated with an elongated optic disc shape and high corneal astigmatism. The axis of corneal astigmatism was correlated with the orientation of the longest disc diameter. The optic disc was significantly (P < 0.05; chi-square test) more often horizontally oval in eyes with a steeper horizontal corneal meridian than in eyes with a steeper vertical corneal meridian. Correspondingly, the disc was significantly (P < 0.05) more often vertically oval in eyes with a steeper vertical corneal meridian than in eyes with a steeper horizontal corneal meridian. CONCLUSIONS: An abnormal optic disc shape is significantly correlated with corneal astigmatism. Especially in young children, if an abnormal optic disc shape is found on routine ophthalmoscopy, refractometry should be performed to rule out corneal astigmatism and to prevent amblyopia. The direction of the longest optic disc diameter can indicate the axis of corneal astigmatism.

Correlation between mean visual field loss and morphometric optic disk variables in the open-angle glaucomas.

PURPOSE: To correlate morphologic changes of the optic disk with mean visual field defect in glaucoma. METHODS: Color optic disk photographs of 302 patients with primary open-angle glaucoma, 53 patients with pseudoexfoliative glaucoma, and 55 patients with normal-pressure glaucoma were morphometrically evaluated. The data were correlated with mean visual field defect. RESULTS: The correlation between mean visual field defect and neuroretinal rim area was similar to a logarithmic function. The visual field deteriorated slightly in the early stage and markedly in the advanced stages of glaucoma. A discrepancy between normal visual field and abnormal optic disk occurred more often in young than in old patients. Neuroretinal rim shape, total rim area, and rim area in the temporal inferior and temporal superior disk sectors correlated best with mean visual field loss. Alpha and beta zones of peripapillary atrophy and diameter of retinal arterioles were less clearly correlated. Calculated rim variables that were corrected for optic disk area did not markedly improve the correlation coefficients. In eyes with normal visual fields, rim shape was the most important disk variable for detecting glaucomatous optic nerve damage. There were no patients with glaucomatous visual field loss and an unremarkable optic disk. CONCLUSIONS: In early glaucoma, changes are more marked in optic disk appearance than in the visual field, suggesting that at least for some patients, for early glaucoma diagnosis, optic disk appearance is more important than perimetry, whereas for follow-up examination, perimetry may be more useful than optic disk morphometry. The most useful planimetric optic disk parameters are neuroretinal rim shape and rim area.

The full-field flicker test in early diagnosis of chronic open-angle glaucoma.

PURPOSE: To evaluate whether the full-field flicker test, a psychophysical test employing full-field flickering stimuli to measure temporal contrast sensitivity, can detect glaucomatous optic nerve damage in patients with increased intraocular pressure and glaucomatous optic disk abnormalities but normal visual fields. METHODS: Temporal contrast sensitivity was determined with a sinusoidally flickering light (frequency, 37.1 Hz) of constant mean photopic luminance (10 cd/m2) presented in a full-field bowl of 58-cm diameter. The prospective study included three groups of individuals: the "preperimetric" glaucoma group of 80 patients with increased intraocular pressure, glaucomatous optic disk abnormalities, and normal visual fields; the "perimetric" glaucoma group of 56 glaucomatous patients with increased intraocular pressure and glaucomatous changes of the optic disk and visual field; and the control group of 96 normal subjects. RESULTS: Temporal contrast sensitivity was significantly (P < .001) lower in the two glaucoma groups than in the control group. In the preperimetric glaucoma group, 34% of the patients (27/ 80) were recognized by the full-field flicker test at a specificity of 99%. For all study subjects, temporal contrast sensitivity decreased significantly (P < .001) with decreasing neuroretinal rim area, enlarging peripapillary atrophy, and diminishing retinal nerve fiber layer visibility. CONCLUSIONS: The full-field flicker test can detect glaucomatous optic nerve damage in patients with increased intraocular pressure, glaucomatous optic disk abnormalities, and normal visual fields. Considering its feasibility, simplicity, quick performance, and low costs, the full-field flicker test may be helpful in clinics and in screening examinations as a supplement to glaucoma diagnosis.

Optic disc morphology in "age-related atrophic glaucoma".

BACKGROUND: This study was performed in order to evaluate whether, in primary open-angle glaucoma (POAG), patients with a different degree of fundus tessellation vary in optic disc morphology and level of intraocular pressure. METHODS: Color stereo optic disc photographs of 562 patients with POAG and a myopic refractive error of less than -8 diopters were morphometrically examined. According to the degree of fundus tessellation, the total group was divided into a tessellated subgroup (n = 256) and a nontessellated subgroup (n = 306), both matched for neuroretinal rim area and refractive error. RESULTS: In the tessellated subgroup, as compared to the nontessellated subgroup, the mean maximal intraocular pressure values were significantly lower, the parapapillary atrophy was significantly larger, the optic cup was significantly more shallow, frequency of disc hemorrhages was lower, the mean visual field defect was significantly more marked, and patient age was significantly higher. Within the whole study group, the degree of fundus tessellation increased significantly (P < 0.005) with decreasing mean maximal intraocular pressure, decreasing optic cup depth, and increasing degree of parapapillary atrophy. In the subgroups with the highest degree of fundus tessellation, parapapillary atrophy was the greatest and the mean maximal intraocular pressure was the lowest compared to other subgroups. CONCLUSION: At the low-pressure end of POAG, marked fundus tessellation is associated with large parapapillary atrophy, shallow disc cupping, mostly concentric emaciation of the neuroretinal rim, and high patient age. The results suggest a distinct subtype of POAG in older patients with relatively low intraocular pressure leading to a mainly diffuse atrophy of the optic nerve.

Optic disc morphology in juvenile primary open-angle glaucoma.

BACKGROUND: The aim of the study was to evaluate whether, in primary open-angle glaucoma (POAG), patients younger than 40 years differ in optic disc morphology from patients older than 40 years. METHODS: Out of a total group of 419 patients with POAG, we formed and compared two subgroups, one consisting of 37 patients with an age of less than 40 years, the other composed of 382 patients with an age equal to or more than 40 years. Both subgroups were matched for neuroretinal rim area. We examined the optic disc morphometrically using stereo disc photographs. RESULTS: The younger subgroup, as compared to the older subgroup, showed deeper and steeper optic disc cupping, concentric emaciation of the neuroretinal rim, a significantly smaller area of parapapillary atrophy, and significantly higher maximal and minimal intraocular pressure measurements (P < 0.001). The size and shape of the optic disc and the diameter of the retinal vessels at the optic disc border did not vary significantly. CONCLUSIONS: In POAG, patients younger than 40 years differ in optic disc morphology from patients older than 40 years. The younger patients with POAG have high minimal and maximal intraocular pressure readings and an optic disc morphology with deep and steep cupping, concentric loss of neuroretinal rim, and an almost unremarkable parapapillary atrophy. POAG in patients under 40 represents chronic high-pressure open-angle glaucoma with mainly diffuse optic nerve damage.

Advanced primary open-angle glaucoma is associated with decreased ophthalmic artery blood-flow velocity.

Recent findings indicate that low-tension glaucoma is associated with impaired ocular blood flow. In the present study we evaluated the blood-flow in the ophthalmic artery in regulated open-angle glaucoma. Using pulsed Doppler sonography (4 MHz), the blood-flow velocity in the ophthalmic artery of 183 eyes of 95 persons with open-angle glaucoma was examined (mean age, 66.6 +/- 14.5 years). The patients showed advanced glaucomatous optic-nerve atrophy (cup-to-disk ratio, 0.74 +/- 0.27) and regulated intraocular pressure (IOP: range, 8-25 mm Hg; mean, 16.4 +/- 3.9 mm Hg). The blood pressure (BP) was 140 +/- 22 (systolic) and 79 +/- 14 mm Hg (diastolic). The control group (84 eyes of 44 persons: mean age, 69.7 +/- 7.7 years; IOP range, 10-22 mm Hg; mean IOP, 15.2-2.6 mm Hg; BP, 143 +/- 20/81 +/- 9 mmHg was matched for age and circulatory risk factors. The vascular resistance index (RIO) was calculated by the equation RIO = (systolic blood velocity-diastolic blood velocity)/systolic blood velocity. We found that the blood velocity in the ophthalmic artery was significantly decreased in glaucomatous eyes in contrast to normal eyes: systolic peak velocity, 36.9 +/- 16.2 cm/s (normal, 40.2 +/- 10.9 cm/s; P < 0.001); diastolic peak velocity 9.9 +/- 4.4 cm/s (normal, 11.7 +/- 4.0 cm/s, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of ocular blood flow during increases of arterial blood pressure.

The blood flow in the uvea in cats and monkeys during acute increases of arterial blood pressure is well controlled by a sympathetic mechanism protecting the eye from overperfusion. Ocular macrocirculation (ophthalmic artery) and ocular microcirculation (iris) were examined in 22 healthy subjects during acute increases of arterial blood pressure induced by physical exercise (125 W). With a data acquisition and storage software in real time mode several parameters of ocular perfusion and systemic functions were measured simultaneously. Blood flow parameters were measured in the ophthalmic artery by pulsed Doppler sonography and in the iris by laser Doppler flowmetry. Systolic, diastolic, and mean velocities of the ophthalmic artery peak velocity pulse curve, the ophthalmic artery mean velocity pulse curve, and the iris velocity pulse curve were estimated off line. The ophthalmic artery mean velocity pulse curve resembles the integrated velocity of all erythrocytes in the vessel including the slowly running cells near the vessel wall. The iris velocity pulse curve was calculated by a special statistic procedure (ALDF). After exercise there was a significant increase in systolic and diastolic blood pressure and heart rate. The pulse curve of the ophthalmic artery showed significantly increased systolic and decreased diastolic velocities. The vascular resistance of the branches of the ophthalmic artery increased significantly. The iridal vasculature showed no significant change in blood cell velocity but an increased vascular resistance. It was observed that the elevated perfusion pressure was associated with an increased vascular resistance and a constant mean blood velocity in the ophthalmic artery and iridal vessels. The parallel elevation of vascular resistance and blood pressure during exercise may be the reason for a constant blood flow in the ophthalmic artery and the iris. This may be accounted for by a sympathetic mechanism for protecting the eye from overperfusion.

Ocular macro- and microcirculation after topical application of clonidine and metipranolol.

We investigated the effect of clonidine (Isoglaucon, an alpha-agonist) and metipranolol (Betamann, a beta-antagonist) on the blood flow in the ophthalmic artery and the anterior uvea of 40 young, healthy volunteers (mean age, 23.5 +/- 2 years) in a prospective, randomized simple blind study. The blood flow in the iris and ciliary body was detected by laser-Doppler flowmetry (bpm, 403a; TSI; wavelength, 780 nm; power, < 1.6 mW). The blood flow in the ophthalmic artery was measured by pulsed Doppler sonography (4 MHz, EME). The blood pressure, pulse respiration, and intraocular pressure (IOP) were recorded. Vascular resistance (RF) was calculated by the equation RF = (RRmean--IOP)/blood flow. Group 1 was treated with a single drop of Betamann (3 mg/ml) applied topically, and group 2 was treated with Isoglaucon (2.5 mg/ml). Measurements were made before and 30 min after application. Both drugs significantly lowered the IOP by about 7% (P = 0.01). Clonidine did not affect the blood velocity in the ophthalmic artery. In group 2 (metipranolol) we found a significant increase in the blood velocity in the ophthalmic artery during the diastolic period (from 11.0 +/- 3.7 to 11.9 +/- 2.2 cm/s, P = 0.05). Both clonidine and metipranolol decreased the iridal blood flow [clonidine, from 9.3 +/- 3.9 to 7.6 +/- 3.1 (flux), P = 0.05; metipranolol, from 7.5 +/- 2.9 to 6.5 +/- 2.6 (flux), P = 0.05]. Vascular resistance in the iris increased under the effect of clonidine (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous measurement of ocular micro- and macrocirculation, intraocular pressure, and systemic functions.

SIMOMIMA (simultaneous measurement of ocular micro- and macrocirculation) is a 32-channel system for display and analysis of biophysical data on ocular perfusion. Using SIMOMIMA in the real-time mode, several parameters of ocular perfusion and systemic functions were simultaneously measured noninvasively and stored during varying periods of measurement; including ocular macroperfusion (pulsed Doppler sonography: ophthalmic artery), ocular microperfusion (laser Doppler flowmetry; iris, ciliary body, choroid), intraocular pressure, cardiac pulse, respiration, and arterial blood pressure. All data were digitalized and stored by a microcomputer for further data processing. With SIMOMIMA in the off-line mode, several parameters of the ocular and systemic circulation may be examined and correlations between them may be calculated, including absolute values for the ophthalmic-artery blood velocity expressed in centimeters per second; the pulse-wave velocity expressed in centimeters per second; relative values for the microcirculatory blood flow of the iris, ciliary body, or choroid; and absolute values for and the time course of the intraocular pressure, heart rate, and respiration rate. In contrast to the ophthalmic-artery pulse curve, the microcirculatory blood flow in the iris showed no obvious synchronization with the ECG or the respiration rate. The blood-cell velocity and the blood content in the iridal meshwork fluctuated with frequencies ranging between 0.5 and 4 Hz. By a special statistical procedure called averaging laser Doppler flowmetry (ALDF), the influence of the pulsations of the arterial blood pressure (diastolic systolic blood pressure) on the iridial blood flow becomes visible.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of nerve growth factor concentrations in human samples by two-site immunoenzymometric assay and bioassay.

Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues.