Stephen M. Drance

Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures

PURPOSE To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma. METHODS One eye of each eligible subject was randomized either to be untreated as a control or to have intraocular pressure lowered by 30% from baseline. Eyes were randomized if they met criteria for diagnosis of normal-tension glaucoma and showed documented progression or high-risk field defects that threatened fixation or the appearance of a new disk hemorrhage. The clinical course (visual field and optic disk) of the group with lowered intraocular pressure was compared with the clinical course when intraocular pressure remained at its spontaneous untreated level. RESULTS One hundred-forty eyes of 140 patients were used in this study. Sixty-one were in the treatment group, and 79 were untreated controls. Twenty-eight (35%) of the control eyes and 7 (12%) of the treated eyes reached end points (specifically defined criteria of glaucomatous optic disk progression or visual field loss). An overall survival analysis showed a statistically significant difference between the two groups (P < .0001). The mean survival time +/-SD of the treated group was 2,688 +/- 123 days and for the control group, 1,695 +/- 143 days. Of 34 cataracts developed during the study, 11 (14%) occurred in the control group and 23 (38%) in the treated group (P = .0075), with the highest incidence in those whose treatment included filtration surgery. CONCLUSIONS Intraocular pressure is part of the pathogenic process in normal-tension glaucoma. Therapy that is effective in lowering intraocular pressure and free of adverse effects would be expected to be beneficial in patients who are at risk of disease progression.

The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma

PURPOSE In a companion paper, we determined that intraocular pressure is part of the pathogenesis of normal-tension glaucoma by analyzing the effect of a 30% intraocular pressure reduction on the subsequent course of the disease. We report an intent-to-treat analysis of the study data to determine the effectiveness of pressure reduction. METHODS One eligible eye of 145 subjects with normal-tension glaucoma was randomized either to no treatment (control) or to a 30% intraocular pressure reduction from baseline. To be eligible for randomization, the normal-tension glaucoma eyes had to show documented progression of field defects or a new disk hemorrhage or had to have field defects that threatened fixation when first presented for the study. Survival analysis compared time to progression of all randomly assigned patients during the course of follow-up from the initial baseline at randomization. In a separate analysis, data of patients developing cataracts were censored at the time that cataract produced 2 lines of Snellen visual acuity loss. RESULTS Visual field progression occurred at indistinguishable rates in the pressure-lowered (22/66) and the untreated control (31/79) arms of the study (P = .21). In an analysis with data censored when cataract affected visual acuity, visual field progression was significantly more common in the untreated group (21/79) compared with the treated group (8/66). An overall survival analysis showed a survival of 80% in the treated arm and of 60% in the control arm at 3 years, and 80% in the treated arm and 40% in the controls at 5 years. The Kaplan-Meier curves were significantly different (P = .0018). The analyses gave different results because of a higher incidence of cataract in the group that underwent filtration surgery. CONCLUSIONS The favorable effect of intraocular pressure reduction on progression of visual change in normal-tension glaucoma was only found when the impact of cataracts on visual field progression, produced largely by surgery, was removed. Lowering intraocular pressure without producing cataracts is beneficial. Because not all untreated patients progressed, the natural history of normal-tension glaucoma must be considered before embarking on intraocular pressure reduction with therapy apt to exacerbate cataract formation unless normal-tension glaucoma threatens serious visual loss.

Glaucoma and vasospasm

AIMS/BACKGROUND To study the vasoactivity of glaucoma patients with four previously described and distinct disc appearances potentially representative of primary open angle glaucoma subgroups. METHODS Patients with pure examples of four glaucomatous optic disc types—focal ischaemic, myopic glaucomatous, senile sclerotic, and those with generalised cup enlargement, were selected. A detailed ophthalmic, systemic, drug, and smoking history was taken from the patients who, in addition, underwent assessment of peripheral vasospasm with a laser Doppler flowmeter. Differences between the groups were evaluated using an analysis of variance, Student’s t test, Pearson’s χ2 test, Fisher’s exact test together with Spearman’s and Pearson’s correlation tests. RESULTS 38 patients with focal ischaemic, 37 with myopic glaucomatous, 24 with senile sclerotic, and 24 with discs characterised by generalised cup enlargement met the selection criteria. The group of patients with focal ischaemic discs contained more women (66% versus 32%–50% in the other three groups; p=0.01) and had a higher prevalence of vasospasm (63% versus 25%–49%; p=0.01), migraine (32% versus 8%–19%; p=0.02), and cold extremities (66% versus 17%–30%; p=0.00003). The group of patients with senile sclerotic discs had a higher prevalence of systemic cardiovascular disease (58% versus 21%–30% in the other three groups; p=0.01) and thyroid disease (21% cf 0%–8%; p=0.01) and although their mean age was greater (76 years cf 55–65 years; p<0.00001) the findings were independent of age. Smoking was unrelated to optic disc type. CONCLUSION Vasospasm, previously associated with normal tension glaucoma, and generalised cardiovascular disease both appear to be specific risk factors for the development of particular subgroups of glaucoma and may be independent of absolute intraocular pressure levels exerting effects in patients with both “normal” or “raised” intraocular pressure. The simple assessment as to whether a glaucoma patient suffers from colder extremities than average appeared to be better at distinguishing the focal ischaemic type of glaucoma than the more complex determination of vasospasm using the laser Doppler flowmeter.

Ability of the heidelberg retina tomograph to detect early glaucomatous visual field loss.

PurposeThe Heidleberg Retina Tomograph provides rapid, reproducible measurements of optic disc topography as well as calculations of disc parameters. We used a stepwise discriminant analysis to determine which parameters were most useful in detecting individuals with early glaucomatous visual field loss. MethodsWe studied one eye in each of 45 normal individuals and one eye in each of 46 individuals with early glaucomatous visual field loss. The appearance of the optic disc was not used for classification purposes so as not to bias the diagnostic determination obtained by the instrument. The data were analyzed using the reference plane of the software version 1.10 and using a method incorporating the height of the papillomacular bundle as reference level with and without age correction. ResultsWe obtained an 89% sensitivity and 78% specificity for the detection of early visual field loss using the standard reference level. The jackknife classification revealed lower sensitivity of 87% and an unchanged specificity of 78%. With the method incorporating the height of the papillomacular bundle as reference level, the sensitivity was 87% and the specificity was 84% for detecting early visual field loss. The jackknife classification revealed a sensitivity of 87% and a specificity of 82%. With the age correction, the sensitivity was 87%, specificity 84% with regular and jackknife classification. With the standard reference level, the important parameters were the third moment and the maximum depth, with the papillomacular bundle reference level volume above reference level added as important, and with age correction, height variation in contour replaced maximum depth in the analysis. ConclusionThree significant shape parameters of the optic disc can be used to detect early glaucomatous visual field loss.

Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma.

Fifty-nine low-tension glaucoma patients were reviewed with respect to asymmetry of intraocular pressure (IOP) and visual field defects. In the presence of unequal IOP the visual field damage is almost always greater on the side with higher mean IOP. However, only 13 of 47 patients with asymmetric visual field defects had a mean IOP difference between the two eyes of greater than or equal to 1 mmHg. Although in the case of IOP asymmetry visual field damage is greater in the eye with higher mean IOP, other factors must also play an important role in the development of visual field defects in low-tension glaucoma.

Diffuse and Localized Nerve Fiber Loss in Glaucoma

To estimate the usefulness of photographs of the retinal nerve fiber layer in demonstrating glaucomatous neural tissue changes, we examined such photographs of 51 patients with glaucoma, 52 patients with ocular hypertension, and 29 normal individuals. The photographs were assessed in a masked fashion. A semiquantitative damage score was given in subsectors of the arcuate, papillomacular, and nasal nerve fiber bundle areas, separately for localized and diffuse loss of nerve fibers. The coefficients of variation of the reproducibility of retinal nerve fiber layer assessment were 0.22 for diffuse damage and 0.11 for localized damage. We detected abnormal retinal nerve fiber layer changes in 48 of the patients with glaucoma, in 27 of those with ocular hypertension, and in five of the normal control subjects. Generalized reduction of nerve fibers with or without localized defects was more common in patients with glaucoma than in those with ocular hypertension whose abnormal findings were primarily localized defects.

The Normal Human Optic Nerve: Axon Count and Axon Diameter Distribution

Computerized image analysis was used to determine the normal axonal count and axon diameter distribution in 12 normal human eyes. Mean axon count per nerve was 969,279 +/- 239,740 and mean axon diameter was 0.72 +/- 0.07 micron. Multiple linear regression disclosed 4909 axons lost yearly (P = 0.08). Statistical analysis did not show a relationship between axon diameter and age or time to fixation. The inferotemporal sector of the nerve had the highest fiber density (P = 0.02). The superonasal nerve had higher mean diameters (P = 0.02). This study may provide a baseline for future pathologic studies.

The Area of the Neuroretinal Rim of the Optic Nerve in Normal Eyes

We randomly photographed 113 eyes in 113 people without ocular disease. The area of the disk and its neuroretinal rim as well as the width of the disk and cup were measured. The measurements were corrected for magnification of each eye by measuring its refraction and axial length. A linear correlation between disk area and neuroretinal rim area was found (r = .75) as well as a correlation between the disk area and the cup area (r = .83). There was no correlation between age and disk area or rim area.

Color Doppler Imaging and Spectral Analysis of the Optic Nerve Vasculature in Glaucoma

PURPOSE We used color Doppler imaging to study blood flow velocity in the central retinal artery and the short posterior ciliary arteries in patients with glaucoma. METHOD Fifty-two patients with chronic open-angle glaucoma, 24 patients with normal-tension glaucoma, and 28 normal subjects were studied. The mean of the peak systolic velocity, the end diastolic velocity, and the resistive index were compared in the three groups. RESULTS Compared with the normal subjects, the patients with chronic open-angle glaucoma showed a statistically significant (P < .05) decrease in the mean end diastolic velocity and an increase in the mean resistive index in all vessels studied. The patients with normal-tension glaucoma showed similar changes, achieving significance most prominently in the central retinal arteries, compared with normal subjects (P < .05). There were no statistically significant differences between the patients with chronic open-angle glaucoma and those with normal-tension glaucoma. CONCLUSIONS Open-angle glaucoma appears to be associated with a decreased mean flow velocity and an increased mean resistive index in the ocular vasculature. These changes are in keeping with possibly compromised circulation in this region.

Various Glaucomatous Optic Nerve Appearances: Clinical Correlations

PURPOSE To study the prevalence of risk factors for glaucoma as well as the pattern of visual field defects and their progression in patients with open angle glaucoma with different and distinct optic nerve appearances. METHODS One thousand seven hundred eleven optic disc stereo photographs of patients with glaucoma and ocular hypertension and of those suspected of having glaucoma were reviewed to identify pure examples of discs with four different optic disc appearances: focal ischemic discs, myopic glaucomatous discs, senile sclerotic discs, and generalized enlargement of the optic cup discs. The clinical charts of the selected patients were reviewed, with emphasis on the presence of predetermined ocular and systemic risk factors. Their automated visual fields also were analyzed. RESULTS Thiry-four patients with focal ischemic discs, 38 with myopic glaucomatous discs, 22 with senile sclerotic discs, and 23 with generalized enlargement of the optic cup discs were selected. Patients with myopic glaucoma and generalized enlargement of the optic cup discs were significantly younger than patients with focal ischemic and senile sclerotic discs. There were more women in the focal ischemic group. Patients with senile sclerotic discs had a significantly higher prevalence of ischemic heart disease; they also had a higher prevalence of systemic hypertension, which did not reach statistical significance. Migraine was 2.5 times more frequent in the focal ischemic group than in the other groups. Intraocular pressure was significantly higher in the generalized enlargement group. The pattern of visual field defect in the four groups also was distinctly different. CONCLUSIONS Patients with different disc appearances, selected only from their disc photographs, showed differences in their demographic characteristics, prevalence of certain systemic risk factors, intraocular pressure levels, and the pattern of their visual field damage. These findings suggest that these various disc appearances probably represent different populations of patients with glaucoma with, possibly, different pathogenic mechanisms.