Glaucoma without ocular hypertension. A clinical study

One hundred eighty-four glaucomatous eyes (125 patients) with visual field defects of Stage I and II in the central visual field were examined with the Octopus perimeter 201, Program 31 or 33, and were divided into 3 groups according to maximum intraocular pressures: (1) low-tension glaucoma (21 mm Hg), (2) glaucoma simplex (22-29 mm Hg), (3) glaucoma simplex (30-39 mm Hg). In these three groups of glaucomatous eyes the cupping of the optic disk, vision and blood pressure were examined and a further check for cardiovascular risk factors was carried out by the internist. All three groups proved to have an equally high incidence of cardiac insufficiency, abnormal EKG changes and diabetes. However, a low systolic blood pressure was found to be the risk factor more often in patients with low-tension glaucoma than with glaucoma simplex. Furthermore, intraocular pressures in the low-tension glaucoma group were higher than those in the normal population. The occurrence of cupping of the optic disk, which is not present with purely vascular optic nerve diseases, and the location of visual field defects in low-tension glaucoma, which is similar to that in glaucoma simplex but different from vascular diseases, as well as the increased diurnal tension variations of diurnal tension curves compared to the normal population are all factors which indicate that low-tension glaucoma is not a purely vascular optic nerve disease, and that pressure-lowering therapy is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)     

Difference of optic disc topography between a low-tension group and a high-tension group in normal-tension glaucoma patients

PURPOSE: Glaucomatous visual field loss and optic disc damage differ by intraocular pressure (IOP) levels. In this study, we compared the optic disc topography in the high-tension group and the low-tension group in normal-tension glaucoma (NTG). METHOD: We selected NTG patients with mean deviation (MD) > or = -10.00 dB and the highest recorded IOP of < 14 mmHg or > or = 17 mmHg without glaucoma treatment. We classified NTG eyes into the following two groups: 1) a low-tension group with the highest recorded IOP of < 14 mmHg, 2) a high-tension group with the highest recorded IOP of > or = 17 mmHg. The optic disc parameters in the low-tension group eyes were compared with those in the high-tension group eyes using a Heidelberg Retina Tomograph. RESULTS: Nineteen eyes of nineteen patients were selected for each group. The cup/disc area ratio in the global sector, and the rim volume in the nasal sector of the low-tension group had deteriorated more than in the high-tension group. CONCLUSIONS: The disc topography is different between the low-tension group and the high-tension group in the nasal sector, suggesting that different pathogenetic mechanisms exist in the optic disc damage in NTG.     

The neurologic evaluation of patients with low-tension glaucoma

One hypothesized cause of low-tension glaucoma is chronic or intermittent ischemia of the optic nerve. Since the optic nerve and brain are both parts of the central nervous system and share a common blood supply, the authors wondered if patients with low-tension glaucoma might also have clinical or radiographic evidence of cerebral atrophy. In this study, 27 patients with low-tension glaucoma were examined using neurobehavioral testing, electroencephalography, computerized tomographic scan, neurological history, and physical examination. In only a small number of patients were these tests abnormal. However, 12 of the 27 patients gave a history of common or classic migraine. This unexpected finding raises the possibility that migraine-related ischemia might be the pathogenic mechanism in some cases of low-tension glaucoma.     

Comparison of visual field defects in the low-tension glaucomas with those in the high-tension glaucomas

We compared the visual fields of 79 eyes (48 patients) with low-tension glaucoma (intraocular pressure less than 21 mm Hg) to the visual fields of 106 eyes (74 patients) with high-tension glaucoma (intraocular pressure greater than 30 mm Hg). Both groups had similar amounts of total field loss as determined by computerized threshold perimetry. Scotomas in the low-tension group had a steeper slope (P less than .001), were significantly closer to fixation (P less than .001), and had greater depth (P less than .001) than those in the high-tension group. These findings suggested that more than one causative factor is important in the production of optic nerve damage in glaucoma.     

A comparison of the blue color mechanism in high- and low-tension glaucoma

Twenty-five eyes of 25 high-tension glaucoma patients and 25 eyes of 25 low-tension glaucoma patients matched for similar visual field defects had their spectral increment threshold measured. Patients with high-tension glaucoma showed significant losses in both chromatic and achromatic sensitivities when compared with low-tension glaucoma patients. The results support the hypothesis that there may be different mechanisms of damage in glaucoma.     

Fluorescein angiography in chronic simple and low-tension glaucoma.

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.     

Optic disk and visual field correlations in primary open-angle and low-tension glaucoma

If the amount of visual field loss is less than expected from the amount of optic disk cupping in low-tension glaucoma compared with primary open-angle glaucoma, it might imply a difference between the two conditions in the type of optic nerve lesion produced. To test this hypothesis, three observers independently examined, in a masked fashion, optic disk stereoscopic photographs of 127 eyes with primary open-angle glaucoma and 71 eyes with low-tension glaucoma. For each stereoscopic photograph the observer predicted whether the visual field loss would be mild, moderate, or severe. The visual field were then classified, according to the number of sectors defective on the Goldmann perimeter chart, as having mild (1 to 15 sectors), moderate (16 to 30 sectors), or severe (more than 30 sectors) visual field loss. For no observer did the frequency of underpredictions or overpredictions in the two conditions differ significantly. The results of this study, thus, did not support the theory that the optic disk damage in primary open-angle glaucoma differs from that in low-tension glaucoma.     

Inter-individual variation in blood supply of the optic nerve head

There is no one standard pattern of the blood supply of the optic nerve head in all human eyes. There is a marked inter-individual variation in the blood supply of the optic nerve head, and the various factors which produce this include variations in (I) the anatomical pattern of blood supply, (II) the pattern of posterior ciliary artery (PCA) circulation (the main source of blood supply to the optic nerve head), and (III) the blood flow. The variations in the pattern of PCA circulation include the variations in (a) number of PCAs supplying an eye, (b) area of supply to the optic nerve head by each PCA, (c) location of the watershed zones between the various PCAs in relation to the optic nerve head, and (d) blood pressure in various PCAs as well as short PCAs. The variations in the blood flow in the optic nerve head can be produced by changes in (i) the intraocular pressure, (ii) mean blood pressure in the capillaries of the optic nerve head and (iii) peripheral vascular resistance. These variations are discussed in detail. A lack of appreciation of these complexities of the blood supply of the optic nerve head in health and disease is responsible for many of the current problems in the understanding of the role of vascular disturbances in anterior ischemic optic neuropathy, glaucoma, low-tension glaucoma and various ischemic disorders of the optic nerve head.     

Comparative study of retinal nerve fiber layer damage in Japanese patients with normal- and high-tension glaucoma

PURPOSE: To look for possible differences in the pattern of retinal nerve fiber layer (RNFL) damage induced by normal- and high-tension glaucoma. METHODS: The study included randomly selected eyes from 27 patients with open-angle, high-tension glaucoma (mean age, 54.7 +/- 15.0 years; range 21-74 years) and from 19 age-matched patients with normal-tension glaucoma (mean age, 55.7 +/- 11.9 years; range 35-83 years). Eyes were examined using scanning laser polarimetry. RESULTS: The ratio between the superior and inferior quadrant thickness, or symmetry, was significantly lower in patients with high-tension glaucoma (1.00 +/- 0.22) than in patients with normal-tension glaucoma (1.18 +/- 0.32). Similarly, the ratio of the superior to the nasal quadrant thickness was significantly lower in patients with high-tension glaucoma (1.56 +/- 0.38) than in patients with normal-tension glaucoma (1.80 +/- 0.29). No statistically significant differences in the other parameters were detected between the two groups. CONCLUSION: These results show that the pattern of RNFL change is different in patients with high- and low-tension glaucoma. The thickness of the RNFL is reduced symmetrically in the superior and inferior quadrants in high-tension glaucoma, whereas a more localized defect on the inferior RNFL occurs in normal-tension glaucoma.     

Quantitative analysis of visual field and optic disk in glaucoma: retinal nerve fiber bundle-associated analysis

 Background: A study was performed to evaluate whether visual field analysis using a perimetric nerve fiber bundle map gives information additional to global visual field indices and cumulative defect curves for early glaucoma diagnosis. Methods: One hundred and four control subjects, 124 patients with ocular hypertension (OHT), 97 patients with high-tension glaucoma without visual field defects (preHTG) and 91 patients with open-angle glaucoma with visual field defects [30 low-tension glaucoma (LTG), 61 high-tension glaucoma (HTG)] were included in this study. Correlation analyses were performed between (a) global visual field indices and total neuroretinal rim (NRR) area; (b) local mean values of four visual field areas and the NRR area of the corresponding four optic disk sectors; and (c) local mean values of 10 perimetric nerve fiber bundles (PNFB1–10) according to Weber and Ulrich (1991) and the four optic disk sectors. The correlations were adjusted for global mean defect and total NRR. Results: There were no significant correlations between NRR area and visual field in control subjects or in patients with OHT or preHTG for all three analyses. Significant correlations were found between the global visual field indices and the total NRR area for LTG and HTG. Significant correlations between local mean defects and NRR area of corresponding optic disk sectors were found only in LTG for the superior and inferior visual field area and the PNFB covering these areas. Conclusion: The method used for visual field analysis and sectorization of the optic disk does not give additional information on visual field defects in patients with normal global visual field indices and a normal cumulative defect curve. The nerve fiber bundle-related visual field analysis allows the topographical determination and quantification of glaucomatous damage. Received: 4 February 1999 Revised: 20 September 1999 Accepted: 4 October 1999     

Erythrocyte deformability in high-tension and normal tension glaucoma

The exact cause of primary open angle glaucoma is still unknown. Intraocular pressure is a major factor but it is impossible to explain the whole mechanism of glaucomatous optic nerve damage with only increased intraocular pressure. Other factors play important roles in the development of glaucoma. With this point of view, vascular factors have been implicated in the pathogenesis of glaucoma.We tried to determine the etiopathogenetic role of decreased erythhrocyte deformability in normal tension glaucoma and high-tension glaucoma. The study group consisted of 16 patients with the diagnosis of normal tension glaucoma, 17 patients with the diagnosis of high-tension glaucoma, and 24 patients as controls.Independent t-tests were used to compare the three groups two by two for age, hematocrit, mean cell volume, plasma protein level, cardiovascular risk factors, and erythrocyte deformability. There was no statistically significant relationship (p > 0.05) between the groups concerning the erythrocyte deformability. When we consider all of 57 patients, we found that both increasing age (> 60 years) and greater mean cell volume (> 84 fl) had a statistically significant relationship with decreased erythrocyte deformability (p < 0.05). When we performed Pearson correlation analysis, we found that only mean cell volume and erythrocyte deformability had a statistically significant relationship (r=0.31, p=0.02).We conclude that decreased erythrocyte deformability is not a major factor in the ethiopathogenesis of normal tension glaucoma and high-tension glaucoma.     

Acquired pits of the optic nerve. Increased prevalence in patients with low-tension glaucoma

The authors studied 232 glaucoma patients in an attempt to shed light on the implications of the pit-like localized cupping of the optic nerve often referred to as an "acquired pit of the optic nerve" (APON) both in low-tension glaucoma and in glaucoma associated with elevated intraocular pressure (IOP). Twenty (74%) of the 27 patients with low-tension glaucoma had APONs, whereas 31 (15%) of the 232 patients with elevated pressure did (P less than 0.001). Overall, there was no difference between the degree of field loss in patients with APONs and in those without. We suggest that APONs may signal an abnormal susceptibility of the optic nerve to the damaging effects of IOP.     

Central corneal thickness in low-tension glaucoma

BACKGROUND: It is possible that the intraocular pressure (IOP) is underestimated in eyes whose central cornea is thinner than normal. The objective of this study was to determine and establish the significance of central corneal thickness in patients with low-tension (normal-tension) glaucoma compared with those with chronic open-angle glaucoma (COAG) or ocular hypertension and healthy eyes. METHODS: The study was carried out from February 1998 to May 1999. Central corneal thickness was measured by ultrasonic pachymetry and IOP was measured by Goldmann applanation tonometry in 25 patients with low-tension glaucoma (untreated IOP less than 21 mm Hg with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 80 patients with COAG (untreated IOP 21 mm Hg or greater with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 16 patients with ocular hypertension (untreated IOP 21 mm Hg or greater, with normal optic nerve head and no history of glaucoma or elevated IOP, and normal visual field on automated perimetry) and 50 control subjects (untreated IOP less than 21 mm Hg with normal optic nerve head and no history of glaucoma or elevated IOP). Analysis with Pearson's product-moment correlation was performed to determine the correlation of IOP and central corneal thickness, and one-way analysis of variance was used to compare corneal thickness between groups. RESULTS: The central cornea was significantly thinner in the low-tension glaucoma group (mean 513.2 mu [standard deviation (SD) 26.1 mu]) than in the COAG group (mean 548.2 mu [SD 35.0 mu]) and the control group (mean 556.7 mu [SD 35.9 mu]) (p < 0.001). No significant difference in corneal thickness was found between the COAG and control groups. The ocular hypertension group had significantly thicker corneas (mean 597.5 mu [SD 23.6 mu]) than the three other groups (p < 0.001). INTERPRETATION: Patients with low-tension glaucoma may have thinner corneas than patients with COAG and healthy subjects. This results in underestimation of their IOP. Corneal thickness should be taken into account when managing these patients to avoid undertreatment.     

Hemorrhage of the optic disc and neurosensorial dysacousia

Forty-one high-tension glaucoma patients. 16 normotensive glaucoma patients, and 30 normals were studied in relationship to neurosensorial dysacousia. Although frequency of dysacousia was higher in normotensive glaucoma (87.5%) in comparison with high-tension glaucoma (75.69%) and normals (76.6%). this was not statistically significant (p = 0.53). When we compared glaucoma patients with and without hemorrhages of disc. 100% of the former had neurosensorial dysacousia and 71.4% of the latter had it (p = 0.047). The association of vascular disease in neurosensorial dysacousia and its association with hemorrhages of the optic disc suggest that there could be a common vascular denominator in both diseases.     

Biostatistical evidence for two distinct chronic open angle glaucoma populations.

Twenty-six eyes of 26 patients with low-tension glaucoma and 34 eyes of 34 patients with high-tension glaucoma were studied. Fifty-one measurements were available on each patient, including visual field indices, finger blood flow measurements, as well as haematological, coagulation, and biochemical and rheological variables. Multivariate analysis revealed two statistically distinct groups of patients, with low and high tension glaucoma cases equally distributed in both. The smaller group (15 patients) showed a suggestion of vasospastic finger blood flow measurements, and had a high positive correlation between the mean deviation (MD) index of field severity and the highest intraocular pressure (r = 0.715, p = 0.0008). The second, larger group (45 patients) showed disturbed coagulation and biochemical measurements, suggestive of vascular disease, and had no correlation between the MD index and the highest intraocular pressure.     

Optic disk evaluation and utility of high-tech devices in the assessment of glaucoma.

BACKGROUND: Every clinician has at one time or another examined a patient who was misdiagnosed as having glaucoma or whose diagnosis of glaucoma was missed. Although glaucoma can exist with normal intraocular pressures, clinicians often rely on the presence of visual-field defects and the degree of optic disk cupping to direct care. However, assessment of cupping is but one small part of optic disk evaluation in glaucoma, and other features of the optic nerve head and retinal nerve fiber layer must be closely inspected to help diagnose borderline cases. In addition, glaucoma can exist without visual-field loss. High-tech devices offer an added dimension in the objective assessment of structure when subjective tests of function and/or ophthalmoscopic observations are equivocal. METHODS: This article details the various parameters of optic disk and retinal nerve fiber layer evaluation and their significance in the assessment of glaucoma. In addition, the role of four high-tech devices is evaluated for their utility in the assessment and progression of glaucomatous damage. CONCLUSIONS: When one attempts to classify a patient as having glaucoma, the degree of cupping and the presence or absence of visual field loss can be misleading. Prior to definitive diagnosis, a thorough evaluation of the optic disk and retinal nerve fiber layer, and appropriate use of high-tech devices, should help reduce the under-diagnosis and overdiagnosis of this disease.     

Obstructive sleep apnea–hypopnea syndrome (OSAHS) and glaucomatous optic neuropathy

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is becoming widely accepted as a risk factor for glaucoma. We discuss the proposed mechanism involved in the pathogenesis of glaucoma in OSAHS, and review the published data on the association between these two conditions, as well as papers regarding functional and structural tests related with glaucomatous damage. There is increasing evidence that the prevalence of glaucoma is higher in OSAHS patients, especially in those with severe disease with apnea-hypopnea index (AHI) >30, and also that sleep disorders may be more frequent in patients with glaucoma, especially in those with normal tension glaucoma (NTG). Several ophthalmic signs and symptoms have been associated with this condition. Raised intraocular pressure (IOP), possibly related to increased body mass index, thinning of retinal nerve fiber layer (RNFL), and alteration of visual field (VF) indices has been demonstrated in many studies, in patients with no history of glaucoma or evidence of glaucomatous changes in the ophthalmic examination. A correlation of AHI with RNFL and VF indices has been described in some studies. Finally, corneal thinning, suspicious glaucomatous disc changes and anomalies in electrophysiological tests such as multifocal visual evoked potential have been described in patients with OSAHS, even in patients with normal findings in the optic nerve and VF, suggesting subclinical optic nerve involvement not detectable in conventional ophthalmic examinations. The pathogenesis of optic nerve involvement has been related to vascular and mechanical factors. Vascular factors include recurrent hypoxia with increased vascular resistance, autonomic deregulation, oxidative stress and inflammation linked to hypoxia and subsequent reperfusion, decreased cerebral perfusion pressure and direct hypoxic damage to the optic nerve. Proposed mechanical factors include increased IOP at night related to supine position and obesity, raised intracranial pressure and elastic fiber depletion in the lamina cribosa and/or trabeculum. In conclusion, ophthalmic evaluation should be recommended in patients with severe OSAHS, and the presence of sleep disorders should be investigated in patients with glaucoma, especially in NTG patients and in those with progressive damage despite controlled IOP, as treatment with continuous positive airway pressure may contribute to stabilizing the progression of glaucomatous damage.     

Visual field defects in patients with normal-tension glaucoma and patients with high-tension glaucoma.

We compared the automated visual field test results of 24 patients with normal-tension glaucoma and 24 patients with high-tension glaucoma who were closely matched for the amount of visual field loss to determine any differences in the characteristics of visual field defects between the two groups. Patients were matched with a maximum allowable difference in mean deviation of 0.3 dB. Although the normal-tension group had a greater amount of focal visual field loss (pattern standard deviation), the difference was not statistically significant (P = .628). Additionally, there was no statistically significant difference in the amount of diffuse or focal visual field damage in the superior hemifields between the two groups; however, the patients with normal-tension glaucoma had a significantly greater amount of localized visual field loss in the inferior hemifield than the patients with high-tension glaucoma (P = .015). Our data support the hypothesis that a vascular mechanism may have a greater role in the pathogenesis of optic nerve damage and visual field loss in patients with normal-tension glaucoma than in patients with high-tension glaucoma.     

Vascular changes within the proximal optic nerve in children suffering from glaucoma

Paraffin-embedded sections of eyes enucleated because of hydrophthalmos (23 cases) or retinoblastoma (59 cases) were examined for vascular changes within the proximal optic nerve. Globes of adults, enucleated because of secondary glaucoma (146 cases), were studied for comparison as well as 19 myopic and 11 microphthalmic eyes enucleated for other reasons, and 19 autopsy eyes of newborns. Microscopic examination revealed an accumulation of dilated thin-walled blood vessels within the septae of the proximal optic nerve of 6 eyes with hydrophthalmos and 11 eyes with retinoblastoma; sometimes the vascular changes appeared somewhat similar to an angioma racemosum. A common finding in all 17 cases was an elevation of the intraocular pressure. There were only 2 cases among the eyes studied for comparison showing dilatations of the optic nerve capillaries: 1 was in a stillborn baby with general hyperemia, and the other was a case of secondary glaucoma in an adult. 9 similar cases have hitherto been published describing vascular dilatations in the optic nerve of children suffering either from glaucoma or retinoblastoma; none of the authors had related these changes to an increased intraocular pressure. It seems likely that hemodynamic changes play an important role in the pathogenesis of these vascular reactions in the proximal optic nerve of infants with flaucoma. A lower arterial blood pressure in infants as well as anatomical and morphological features may be further factors of significance.     

Visual field change in low-tension glaucoma over a five-year follow-up

There is some evidence that the nature and progression of disease in low-tension glaucoma may be distinct from other open-angle glaucomas. The authors assessed visual field change by retrospective case review of all patients treated for low-tension glaucoma by the Glaucoma Service, Wills Eye Hospital, for at least 5 years. Sixty-two glaucomatous eyes of 36 patients were identified. All eyes were treated medically and 40 (65%) underwent at least one surgical procedure. Twenty-eight eyes (47%) had initial field loss confined to a single hemi-field and in the remainder both hemi-fields were involved. Thirty of 57 eyes (53%) showed progression at 3 years and 38 (62%) of 57 had progressed by 5 years. A dense scotoma extending from the nasal periphery toward fixation was the most common visual field defect. The rate of field change in this population is significantly greater than in a cohort of primary open-angle glaucoma patients also seen at Wills Eye Hospital, but who had elevated intraocular pressures. Patterns of field loss and rate of progression in this low-tension glaucoma population suggest that the natural history of low-tension glaucoma differs from high-tension open-angle glaucoma.