Gabriele C. Gusek

Optic disc morphometry in chronic primary open-angle glaucoma. I. Morphometric intrapapillary characteristics.

Four hundred twenty-seven optic discs of 233 unselected patients suffering from chronic primary open-angle glaucoma were morphometrically evaluated and compared with the optic nerve heads of 253 unselected normal subjects. Only one randomly chosen eye per patient was taken into consideration. We found that glaucoma leads to a change in the characteristic configuration of the neuroretinal rim that in normal eyes is significantly (P < 0.001) largest at the lower disc pole, smaller at the upper and nasal disc side, and smallest in the temporal disc region. Based on this information, significant (P < 0.001) morphometric differences between “early” glaucomatous and normal discs are: (a) the neuroretinal rim area in the lower temporal disc sector is smaller than in the upper temporal disc sector; the smallest rim width is outside the horizontal temporal disc sector (“pathognomonic”); the quotient of horizontal to vertical c/d ratio is lowered; and (d) the lower temporal, upper temporal, and total rim area are decreased. No significant difference in overall optic disc size and form exists between normal and glaucomatous eyes. Smaller optic nerve heads are not more susceptible to glaucoma.

Optic disk morphometry in high myopia

The optic nerve head in highly myopic eyes is distinctly different from normal optic disks. We performed magnification-corrected morphometry of photographs of 51 optic nerve heads in highly myopic eyes (myopic refraction of more than −8.00 diopters). Mean refraction was −15.49 ± 5.76 diopters (range, −8.00 to 28.00 diopters), mean age 63.0 ± 12.1 years (range, 27–87 years). The disks were significantly (P < 0.000001; Wilcoxon-Mann-Whitney test) larger and more ovally configurated than 457 unselected normal optic nerve heads with a myopic refraction of less than −8.00 diopters. Refraction, size of the disk, and area of the parapapillary region with chorioretinal atrophy were significantly (P < 0.00001) correlated with each other. The parapapillary vessel diameter was independent from the disk size. Highly myopic disks can be regarded as secondary acquired macrodisks, the size of which is correlated with refraction and possibly age. They should be differentiated from secondary, acquired macrodisks in congenital glaucoma and from primary macrodisks. As in normal eyes, the parapapillary vessel caliber can be used to estimate the optic disk size in relative and approximately absolute units.

Pseudoglaucomatous physiologic large cups

Using planimetric analysis of stereoscopic optic disk photographs, we studied 21 optic nerve heads of 11 subjects who shared the common feature of optic cups that were larger than the mean + 2 S.D. within the normal population. A comparison of these findings to those of 571 normal optic disks and 706 optic nerve heads in eyes with chronic primary open-angle glaucoma showed the following morphologic characteristics: (1) abnormally large optic disk area (mean +/- S.D., 4.49 +/- 0.56 mm2), (2) large cup/disk ratios with the horizontal ratio (0.78 +/- 0.03) significantly (P less than .001) larger that the vertical (0.71 +/- 0.03), (3) increased incidence of cilioretinal arteries, (4) normal neuroretinal rim area (2.06 +/- 0.35 mm2), (5) normal neuroretinal rim configuration, inferiorly (0.43 +/- 0.08 mm) broader (P less than .001, Wilcoxon test) than superiorly (0.33 +/- 0.06 mm), smallest (P less than .0001) temporally (0.20 +/- 0.04 mm), (6) normal form of zone alpha (irregular hypopigmentation and hyperpigmentation) of the parapapillary chorioretinal atrophy with its widest extension in the temporal horizontal area, (7) no zone beta (visible large choroidal vessels and sclera), (8) normal caliber of the parapapillary retinal vessels, and (9) normal parapillary retinal nerve fiber layer. These characteristics are helpful in the differentiation of primary and secondary large cups.

Size of the optic nerve scleral canal and comparison with intravital determination of optic disc dimensions

Diameters, area, and form of the optic nerve scleral canal were measured in 107 freshly enucleated, unfixed, human donor eyes. Macrophotographs of the sectioned posterior fundus pole were provided with a millimeter scale and evaluated planimetrically. They revealed a surprising variation: area: 2.59 ± 0.72 mm2 (minimum 0.68 mm2, maximum 4.42 mm2); minimal diameter: 1.67 ± 0.72 mm; maximal diameter: 1.92 ± 0.32 mm. The mean form factor was 0.92 ± 0.11 and the quotient of minimal to maximal diameter 0.86 ± 0.11, indicating a slightly oval nearly round form. The coefficients of variation of the methods reproducibility were 0.005 for intraobserver and 0.02 for interobserver determination. The size values of these optic nerve scleral canals were not significantly (Wilcoxon-Mann-Whitney test) different from than those of 100 unselected optic discs that had been determined intravitally using Littmanns method. This indicates the reliability of Littmanns method for the intravital measurement of the optic nerve head in absolute dimensions.

Variability of the real dimensions of normal human optic discs

Using Littmanns method for correcting the magnification of central fundus photographs, we evaluated planimetrically the color slides of 88 unselected optic discs without evidence of any optic nerve disease. High myopes (< −8.00 diopters) had been excluded. Mean optic disc area measured 2.89 ± 0.76 mm2 (minimum 0.86 mm2, maximum 5.39 mm2), mean cup area 0.63 ± 0.64 mm2 (minimum 0.00 mm2, maximum 3.10 mm2) and mean neuroretinal rim area 2.26 ± 0.58 mm2 (minimum 0.86 mm2, maximum 3.84 mm2). Horizontal disc diameter ranged from 0.91 mm to 2.42 mm (mean 1.79 ± 0.27 mm) and vertical diameter from 1.08 mm to 2.76 mm (mean 1.97 ± 0.29 mm). Coefficients of variation of the methods reproducibility were 0.03 for intraobserver and 0.03 for interobserver determination. Regarding the Gaussian distribution curve based on these preliminary data, microdiscs can be defined as being smaller than 1.4 mm2 (mean minus two standard deviations) and macrodiscs as being larger than 4.4 mm2 (mean plus two standard deviations).

Radiation therapy of optico–hypothalamic gliomas (OHG) – radiographic response, vision and late toxicity

BACKGROUND Management strategies for optic pathway gliomas include observation, surgery, irradiation, chemotherapy and a combination of these modalities. It has been the policy of our University Hospital to consider radiation as the standard treatment for progressive optic pathway gliomas. This report describes the clinical presentation, treatment patterns and outcome with special emphasis on the long term functional status of patients with optico-hypothalamic gliomas (OHG). PATIENTS AND METHODS Between 1975 and 1997, 25 patients with OHG were treated by radiation therapy (RT) following surgery or biopsy. All patients received a local RT with a 0.5-1 cm margin around the lesions as depicted on CT or MRI scans. Age adjusted radiation doses ranged from 45 to 60 Gy with a single fraction size of 1.6-2 Gy. Endpoints of the study were: radiographic response, survival, progression-free survival and time to endocrinologic toxicity as well as the visual function during follow-up. The median follow-up time was 9 years (range, 1.5-23 years). RESULTS A partial response was noted in six (24%) of the patients, 13 (52%) patients had a stable tumour throughout the observation period and six (24%) patients had a tumour progression. Overall survival and progression-free survival rates were 94 and 69% at 10 years, respectively. A significant influence on progression-free survival was noted for age at diagnosis (P=0.04) and total dose (P=0.05). Nine out of 13 (69%) patients aged below 10 years compared with 3/12 (25%) patients aged above 10 years experienced hypothalamic-pituitary deficiency (P=0.008) during follow-up. As for visual acuity, nine patients had an improvement, another 13 patients a stable situation and three patients a measurable deterioration. Visual field deficits improved in three, remained unchanged in 16 patients and worsened in only one patient. CONCLUSION Postoperative RT with a total dose above 45 Gy should be considered as standard treatment in OHG with documented progression. Close radiographic monitoring and lifelong yearly evaluation for the need of possible hormone replacement are strongly recommended.

Optic disc morphometry in chronic primary open-angle glaucoma II. Correlation of the intrapapillary morphometric data to visual field indices*

The intrapapillary morphometric data of 290 optic nerve heads of 158 patients with chronic primary open-angle glaucoma and of 253 unselected normal subjects were correlated with the visual field indices of Octopus program 32,34-Delta. Only one eye per patient was considered. Significant correlations (P < 0.001) were revealed for the neuroretinal rim (NRR) area as a whole and in four defined disc sectors, the ratio of lower temporal to upper temporal rim area, the rim width, the optic cup area and diameters, the horizontal and vertical cup/disc (c/d) ratios, and the quotient of horizontal to vertical c/d ratio. Correlation coeffcients ranged between 0.30 and 0.77. They were highest for the rim area of the inferior temporal disc sector, followed by the superior temporal, nasal, and temporal sectors. There were no correlations for the optic disc size and form. The topographic morphometry of the intrapapillary optic disc structures was unremarkable in four glaucomatous eyes with small discs.

Optic nerve head drusen associated with abnormally small optic discs

SummaryUsing Littmanns method for correcting the magnification of central fundus photographs we evaluated the absolute optic disc size in 26 eyes with visible optic nerve head drusen. The optic nerve head area in these eyes (1.79 + −0.50mm2) was significantly smaller (p<0.001) than normal standard values previously determined (2.89 + −0.76 mm2). The drusen were most commonly located and most densely packed at the upper and lower optic disc border. The coefficients of variation of the methods reproducibility were 0.06 for intraobserver and 0.11 for interobserver determination.The abnormally small optic disc indicating an abnormally small optic nerve scleral canal may inhibit by mechanical compression the axonal flow within the optic nerve fibers. This may ultimately lead to drusen formation. Pseudoneuritis also associated with an abnormally small optic disc may be a preceder of acquired optic nerve head drusen.

Anterior ischemic optic neuropathy: Nonarteritic form in small and giant cell arteritis in normal sized optic discs

SummaryBy estimating cup/disc ratios in fellow eyes it has been assumed that nonarteritic anterior ischemic optic neuropathy (AION) occurs more often in small optic nerve heads. Correcting the photographic magnification we used absolute size units to measure 33 affected and 25 fellow optic discs with nonarteritic AION and 7 affected and 7 fellow optic nerve heads with arteritic AION.The affected and fellow discs with nonarteritic AION (2.37 + -0.29 mm2 and 2.31 + -0.31 mm2) were significantly (p<0.001, Mann-Whitney-test) smaller than 457 normal optic nerve heads (2.69 +-0.70 mm2). They were significantly (p<0.001; Mann-Whitney-test) larger than optic nerve heads with pseudopapilledema or drusen. Affected and fellow optic nerve heads with arteritic AION were not significantly different in size from normal discs but significantly (p<0.005) larger than the discs affected by nonarteritic neuropathy. There were no significant form differences between the pathologic and normal discs.Optic disc morphometry can be helpful in the differentiation of nonarteritic and arteritic AION: Non-arteritic AION occurs more often in small optic discs, arteritic AION is more often in normal sized optic nerve heads.

Correlations of the Neuroretinal Rim Area with Ocular and General Parameters in Normal Eyes

The neuroretinal rim as equivalent of the retinal nerve fibers is the target in the evaluation of glaucomatous optic nerve heads. Its area was measured in absolute size units using photographs of 234 normal optic disks and correcting the photographic magnification according to Littmanns method. High myopic eyes (less than -8.00 dptr) were excluded. The mean rim area was 2.09 +/- 0.60 (0.80-3.80 mm2). It was significantly correlated (p less than 0.00001) to the optic disk area. In optic disks without cupping, the neuroretinal rim area was identical with the disk area (r = 1.0, slope of the regression line = 1.0). In disks having cups with temporal flat slopes, the rim area increased by a factor of 0.71 with the disk size, in disks with circular steep cups, by a factor of 0.26. This interindividual variability and the correlations between rim and disk area might be clinically important for morphometry of glaucomatous optic nerve heads. There were no significant correlations between rim area and age, sex, refraction or axial length.