Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study

OBJECTIVE: To assess the impact of vascular risk factors on the prevalence of primary open angle glaucoma. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Four thousand two hundred ninety-seven patients more than 40 years of age underwent a complete ocular examination in the context of the Egna-Neumarkt Glaucoma Study. INTERVENTION: Ocular examinations were performed by trained, quality-controlled ophthalmologists according to a predefined standardized protocol including medical interview, blood pressure reading, applanation tonometry, computerized perimetry, and optic nerve head examination. MAIN OUTCOME MEASURES: Prevalences of ocular hypertension, primary open-angle glaucoma, normal-tension glaucoma, and other types of glaucoma were determined. Correlation coefficients were calculated for the association between systemic blood pressure and age-adjusted intraocular pressure (IOP) and between age and both intraocular and systemic blood pressures. Odds ratios were computed to assess the risk of primary open-angle glaucoma and normal-tension glaucoma in relation to systemic hypertension or antihypertensive medication, blood pressure levels, diastolic perfusion pressure, and a number of other cardiovascular risk factors. RESULTS: A positive correlation was found between systemic blood pressure and IOP, and an association was found between diagnosis of primary open-angle glaucoma and systemic hypertension. Lower diastolic perfusion pressure is associated with a marked, progressive increase in the frequency of hypertensive glaucoma. No relationship was found between systemic diseases of vascular origin and glaucoma. CONCLUSIONS: Our data are in line with those reported in other recent epidemiologic studies and show that reduced diastolic perfusion pressure is an important risk factor for primary open-angle glaucoma.     

Beta-blocker eyedrops and nocturnal arterial hypotension.

PURPOSE: To investigate the effects of topical beta-blocker eyedrops on nocturnal arterial hypotension and heart rate and on visual field deterioration. METHODS: We prospectively investigated 275 white patients, 161 with glaucomatous optic neuropathy and 114 with nonarteritic anterior ischemic optic neuropathy, by 24-hour ambulatory blood pressure monitoring and diurnal curve of intraocular pressure, in addition to detailed ophthalmic evaluation. Of the patients with glaucomatous optic neuropathy, 131 had normal-tension glaucoma and 30 had primary open-angle glaucoma. Of the 275 patients, 114 were using topical beta-blocker eyedrops twice daily (76 with normal-tension glaucoma, 26 with primary open-angle glaucoma, and 12 with anterior ischemic optic neuropathy). RESULTS: Hourly average blood pressure data analyses showed overall a drop in blood pressure as well as heart rate during sleep, and a significantly greater drop in mean diastolic blood pressure (P = .009) at night in normal-tension glaucoma than in anterior ischemic optic neuropathy. Also, patients using beta-blocker eyedrops experienced a significantly greater percentage drop in diastolic blood pressure at night (P = .028), lower minimum nighttime diastolic blood pressure (P = .072), and lower minimum nighttime heart rate (P = .002) than did those not using them. In normal-tension glaucoma, eyes receiving beta-blocker eyedrops showed visual field progression significantly (P = .0003) more often than those not receiving beta-blockers. CONCLUSIONS: The findings of our studies, as well as those of others, suggest that any factor that increases nocturnal arterial hypotension is a potential risk factor in vulnerable individuals with glaucomatous optic neuropathy or anterior ischemic optic neuropathy. The present study suggests that the use of beta-blocker eyedrops, by aggravating nocturnal arterial hypotension and reducing the heart rate, may be a potential risk factor in susceptible individuals.     

High prevalence of glaucoma in patients with sleep apnea syndrome.

OBJECTIVE: To determine the prevalence of glaucoma in sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 114 white patients consecutively referred for polysomnographic evaluation of suspected SAS. INTERVENTION: Complete ophthalmologic examination, including computerized perimetry and simultaneous stereoscopic optic disc photographs. MAIN OUTCOME MEASURES: Spearman rank correlations between the respiratory disturbance index during night sleep (RDI), a value used to diagnose and grade SAS, and visual acuity, intraocular pressure (IOP), visual field indices, presence or absence of glaucomatous optic disc changes, and diagnosis of glaucoma. Each correlation was controlled for age and body mass index. To compare proportions of patients harboring glaucoma, the binomial test was used. RESULTS: Sixty-nine (60.5%) of the 114 patients had an RDI > or =10, which indicates SAS. Three patients had primary open-angle glaucoma, and two had normal-tension glaucoma. All patients with glaucoma had SAS. The observed prevalence of glaucoma in patients with SAS (5 of 69, 7.2%) was significantly higher than expected in a white population (2%) (P = 0.01). The RDI correlated positively with IOP (P = 0.025), visual field loss variance (P = 0.03), glaucomatous optic disc changes (P = 0.001), and diagnosis of glaucoma (P = 0.01). CONCLUSIONS: Patients with SAS constitute a high-risk population for glaucoma and should therefore be screened for glaucoma.     

Determination of individually endurable intraocular pressure (pressure of target) in primary glaucoma

On the basis of ocular perfusion pressure a new method was suggested for determining an individually endurable intraocular pressure (IOP), i.e. pressure of target. A total of 390 eyes (232 patients with primary open-angle and normal-tension glaucoma) were examined before and after conservative and surgical treatment. The pressure of target was found, in a progressing worsening of visual functions, to be significantly lower versus the stabilized glaucoma, which was due to a low ocular perfusion pressure. The maximally tolerable IOP in a progressing glaucomatous optic neuropathy concomitant with a normalized IOP amounts to 13-15 mm Hg; while, in the stabilized glaucoma it can exceed the mean statistic norm. The pressure of target was shown to be a non-permanent value, which changes depending on the dynamics of the ophthalmic perfusion pressure and IOP. The sensitivity of the suggested method is 77.4%. It can be used in prognosticating the glaucomatous-process clinical course and in choosing an optimal tactics for the treatment of open-angle and normal-tension glaucoma.     

Sequential office pressure measurements in the management of glaucoma

PURPOSE: To evaluate the usefulness of day-long sequential office measurements of intraocular pressure (IOP) to make therapeutic decisions in patients with progressive glaucomatous damage despite apparently 'controlled' IOP. METHODS: We reviewed the records of 93 consecutive glaucoma patients (185 eyes) who underwent sequential office IOP measurements (every hour from 7 AM to 5 PM on a single day). These included 53 patients with normal-tension glaucoma (NTG), 12 glaucoma suspects (GS), and 28 patients with primary open-angle glaucoma (POAG) whose visual field deteriorated despite apparently 'controlled' IOP. Only one eye per patient was included in the study. RESULTS: The pattern of the day-long IOP curve was similar in the 3 groups of patients. IOPs were highest in the early morning hours in all groups. The mean +/- SD of the IOP range was 5 +/- 2 mm Hg. An IOP > 21 mm Hg was found in 3 eyes (3%), whereas a range of IOPs > 5 mm Hg was detected in 33 eyes (35%). In the NTG group, there was a significant correlation between visual field deterioration and the peak and range of IOP (P = 0.0002 and P = 0.05, respectively). CONCLUSIONS: Day-long sequential office IOP measurements are useful in selected patients who demonstrate progressive glaucomatous damage. Early morning measurements are most frequently highest. The range of IOP may be as important, or more important than, the peak IOP level.     

Effect of hospitalization on intraocular pressure in patients with high tension and normal tension glaucoma

PURPOSE: To determine the effect of hospitalization on intraocular pressure (IOP) in glaucoma patients. DESIGN: Prospective case series. METHODS: IOP was measured on three consecutive days in 26 high-tension (HTG) and 13 normal-tension (NTGwm) glaucoma patients under IOP-lowering treatment, and in 28 normal-tension glaucoma patients without IOP-lowering treatment (NTGnm), and change was compared by analysis of variance. RESULTS: IOP decreased significantly, but comparably, in the three groups and between right and left eyes, although, the relative change to IOP on day 1 was significantly less pronounced in the group without treatment on day 2 and 3 compared with the treated groups. CONCLUSIONS: Glaucoma patients showed a significant decrease in IOP during hospitalization. Although this decrease was more pronounced among the treated patients, it was also present in nontreated patients. Consequently, other factors than improved compliance during hospitalization must play a role in this phenomenon.     

Comparison of ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost

PURPOSE: To compare the ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost monotherapy. METHODS: In prospective randomized fashion, we evaluated the ocular hypotensive effect and safety of brinzolamide or timolol in 1 eye of 32 patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had been treated with latanoprost for more than 1 month. Intraocular pressure (IOP), blood pressure, and pulse were measured before and at 4, 8, and 12 weeks. Corneal endothelial cell density was measured at baseline and at 12 weeks. RESULTS: The IOP was 17.8+/-1.7 mm Hg (mean+/-SD) before the addition of brinzolamide (n=15) and 15.7+/-2.1 mm Hg at 12 weeks (P<0.01). In comparison, the IOP was 18.5+/-3.7 mm Hg before the addition of timolol (n=15) and 15.8+/-3.2 mm Hg at 12 weeks (P<0.01). Both brinzolamide and timolol significantly decreased IOP at 12 weeks, by a mean of 2.0 mm Hg and mean 2.7 mm Hg, respectively, and were more effective than latanoprost alone (P<0.01), but there were no significant differences between the drugs and no significant differences in corneal endothelial cell density and blood pressure before and after addition of either drug. At 12 weeks, pulse was decreased in patients receiving timolol (P<0.01). As systemic adverse events, there was one instance of malar flushing after brinzolamide addition and episodes of chest discomfort after timolol addition in 1 patient. Ocular adverse events were slight. CONCLUSIONS: Brinzolamide and timolol added to latanoprost have similar ocular hypotensive effects and safety in primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension.     

Episcleral venous pressure in untreated primary open-angle and normal-tension glaucoma

The aim of this prospective study was to investigate episcleral venous pressure (EVP) in different forms of glaucoma in comparison with age-matched controls. EVP was measured by means of a venomanometer in 32 eyes with untreated primary open-angle glaucoma (POAG), 36 eyes with untreated normal-tension glaucoma (NTG) as well as 56 control eyes without ophthalmological disease other than cataract. In addition to ophthalmological standard examination, cardiovascular parameters such as systolic and diastolic blood pressure and heart rate were recorded. In the POAG group, EVP was 12.1 +/-0.5 mm Hg and in the NTG group 11.6 +/- 0.4 mm Hg. This was significantly different from EVP of the controls (9.5 +/- 0.2 mm Hg). The EVP/intraocular pressure (IOP) ratio was significantly different in NTG patients (80.0% +/- 3.2) in comparison with both POAG patients (67.1% +/- 2.8) and controls (69.2% +/- 2.4). The difference between IOP and EVP (IOP - EVP) was 6.2 +/- 0.6 in the POAG, 3.1 +/- 0.45 in the NTG and 4.5 +/- 0.4 in the control group. All these values were significantly different from each other. Regression analysis revealed a significant linear correlation between EVP and IOP in both the NTG and the POAG group. In the control group, however, the correlation was weak. This study is the first to demonstrate differences in EVP between untreated NTG and POAG and an age-matched healthy control group.     

Open-angle glaucoma clinical presentation and management]

Both primary open-angle and normal-tension glaucoma belong to an identical spectrum of diseases. Clinical presentations of primary open-angle or high-tension glaucoma (POAG) and normal-tension glaucoma (NTG) were studied in an attempt to determine prognostic, clinical factors and define the appropriate management. Clinical data obtained from 826 primary open-angle and normal-tension glaucoma patients were analyzed. In addition, the results of laboratory studies, including the immunological assay of heat shock protein (hsp) and gene analyses which were undertaken to identify risk factors at the molecular level, are discussed. 1. The identified prognostic factors were disk hemorrhage, peripapillary chorioretinal atrophy (PPA), maximum intraocular pressure (IOP), the recovery rate of skin temperature after exposure to cold, family history of glaucoma, systemic systolic channel blood pressure, and oral administration of Ca(2+)-channel antagonists. 2. Disk hemorrhage was observed in 30.5% of NTG patients and 15.4% of POAG patients. Cumulative probability of hemorrhagic events was 16.9% in POAG and 38.4% in NTG patients at the end of a 14.8-year follow-up. 3. The hazard ratio of disk hemorrhage decreased with the increase of IOP(26%/5 mmHg) and was 1.46 times higher in females than in males. Disk hemorrhage was closely associated with PPA: PPA becomes greater in association with the progression of glaucomatous optic neuropathy in both POAG and NTG. No such correlation was noted in primary angle-closure glaucoma. 4. Color Doppler imaging analyses and the hourly determination of ocular perfusion pressure (OPP) indicated a difference in retrobulbar hemodynamics between OPP-mean deviation concordant and OPP-mean deviation discordant patients: a circulatory disturbance causally unrelated to OPP seems to be involved in the OPP-mean deviation discordant patients. 5. The oral administration of Ca(2+)-channel antagonists was shown to favorably influence retrobulbar hemodynamics in NTG patients. 6. Serum antigen titer to hsps(hsp 27, alpha B crystallin, human & bacterial hsp 60) was higher in both POAG and NTG patients than in normal subjects. None of the hsp-antigens was correlated to any morphometric parameters of the optic disk or any global indices of the visual field. 7. Myocilin mutation was noted in only 0.5% of POAG patients and 2.37% of NTG patients. The very low rate of occurrence precludes the value of mutation of the gene as a prognostic factor in open-angle glaucoma(OAG). 8. IOP reduction achieved by mitomycin-C trabeculectomy is effective in maintaining visual function in OAG eyes. 9. Brovincamine fumarate is effective in inhibiting the progression of glaucomatous field loss in NTG.     

Is open‐angle glaucoma caused by impaired cerebrospinal fluid circulation: around the optic nerve?

Chronic open-angle glaucoma is the most frequent type of glaucoma and a leading cause for blindness. The role of intraocular pressure (IOP) in the pathogenesis of open-angle glaucoma has been challenged by patients with typical glaucomatous optic disc changes and visual field loss in whom the IOP never exceeded normal values (normal-tension glaucoma), as well as by patients with persistently elevated IOP who do not develop glaucomatous disc or field changes. Recent research has demonstrated that the cerebrospinal fluid (CSF) is not evenly distributed in all CSF spaces and that the subarachnoid space of the optic nerve can turn into a CSF compartment on its own. The biochemical components in this optic nerve compartment can differ markedly from normal CSF and some of its components (such as L-PGDS) may produce a toxic effect on the optic nerve and may therefore play an important role in the pathophysiology of open-angle glaucoma.     

Bradykinin sensitivity in primary open-angle glaucoma and normal-tension glaucoma patients

PURPOSE: To report the reaction after intradermal injection of bradykinin in nonglaucoma, primary open-angle glaucoma, and normal-tension glaucoma subjects. DESIGN: Prospective comparative study. METHODS: The study participants were 14 healthy control subjects, 16 patients with primary open-angle glaucoma, and 15 patients with normal-tension glaucoma. In each participant, the wheal response to intradermal injection of 10 microg bradykinin in the volar forearm was measured by a masked observer. RESULTS: There was no significant difference in the wheal response to bradykinin between control subjects and primary open-angle glaucoma patients (P =.73) and between primary open-angle glaucoma patients and normal-tension glaucoma patients (P =.09). However, there was a significant difference in the wheal response to bradykinin between control subjects and normal-tension glaucoma patients (P =.04). CONCLUSIONS: These in vivo structure-activity studies may suggest abnormalities of the tissue kallikrein-kinin system in normal-tension glaucoma.     

Reversal of intraocular pressure increases with 0.5% apraclonidine after dilated fundus examination in patients with chronic open-angle glaucoma.

BACKGROUND: Apraclonidine 1.0% has been shown to reverse the potential intraocular pressure (IOP) increase after pupil dilation IOP increases in patients with chronic open-angle glaucoma. However, it is only approved for preventing IOP spikes after laser surgery. The purpose of this study is to determine the effectiveness of 0.5% apraclonidine in reversing IOP increases after pupillary dilation in patients with chronic open-angle glaucoma. METHODS: Twenty-two patients with chronic open-angle glaucoma were found to have an increase in post-dilation IOP of at least 4 mmHg from pre-dilated levels (baseline) in both eyes. IOP was measured 1 hour after dilation, after which two drops of 0.5% apraclonidine were instilled in one eye and the IOP was remeasured 15 minutes later in both eyes. Instillation of 0.5% apraclonidine in one eye was continued every 15 minutes and IOP was measured 15 minutes after each instillation, until the pressure returned to baseline levels. RESULTS: The IOP of the initially treated eye of all 22 patients returned to within levels clinically insignificant from baseline IOP within 90 minutes. By comparison, the IOP of the control group (untreated eye) remained elevated. Once the initial treatment eye returned to baseline levels, the control group was then treated with 0.5% apraclonidine, resulting in a lowering effect of the IOP in similar fashion to the initial treated group. CONCLUSIONS: Apraclonidine 0.5% appears to be effective in reduction of post-dilated IOP increases in patients with chronic open-angle glaucoma.     

Color doppler imaging in glaucoma patients with asymmetric visual field loss

With color Doppler imaging, we attempted to determine whether glaucoma patients with asymmetric visual field losses had evidence of asymmetric blood flow velocities in the central retinal artery despite similar intraocular pressure (IOP) curves in both eyes. We found that eyes with more severe visual field damage had an increased local resistance to blood flow in the central retinal artery. Thus vascular factors might have important roles in the pathogenesis of primary open-angle glaucoma.     

Basic and clinical studies of pressure-independent damaging factors of open angle glaucoma

Pathogenesis of open-angle glaucoma involves both pressure-dependent damaging factors and pressure-independent damaging factors. The high prevalence of open-angle glaucoma with normal pressure (normal-tension glaucoma) in Japan implies that treatment of pressure-independent damaging factors in Japanese open-angle glaucoma patients is of importance. In an attempt to investigate the roles of pressure-independent damaging factors in open-angle glaucoma, we carried out basic and clinical studies and obtained the following results. 1. The rate of deterioration of visual field after trabeculectomy in normal tension glaucoma patients with post-operative intraocular pressure (IOP) of 10 mmHg was found to be -0.25 dB/year of mean deviation (MD), suggesting that contribution of pressure-independent damaging factors to the deterioration of MD in open-angle glaucoma is around -0.25 dB/year of mean deviation (MD). 2. Experiments using isolated purified cultured retinal ganglion cells (RGCs) indicated that calcium-channel blockers and some of antiglaucoma drugs showed neuroprotective effects on RGCs at concentrations of 0.01 microM or higher. 3. In mice, damage to RGCs resulted in secondary degeneration of neurons and activation of glial cells in the lateral geniculate nucleous (LGN) and superior colliculus, and these secondary changes in the central nervous system (CNS) due to RGC damage was partly ameliorated by systemic administration of memantine. 4. Mice experimental high IOP glaucoma models could be established using laser irradiation of the limbal area, and the usefulness of Tonolab in IOP measurements of mice eye was confirmed. 5. Monkey experimental high IOP glaucoma models revealed that in the glaucomatous optic nerve head vaso-constrictive reactions to an alpha-1 agonist was abolished, while vasodilative reaction to a prostaglandin FP receptor agonist was retained. 6. In monkeys with experimental high IOP glaucoma, secondary damage to neurons in the LGN and the glial reaction to it were also found, similar to the mice experiments. In living monkeys the glial reaction in the LGN could be observed by means of positron emission tomography. 7. In the LGN of monkeys with experimental high IOP glaucoma, the M-cell system was preferentially damaged in the early stage, while in the later stages both the M- and P-cell systems were damaged. 8. In a single-instituted prospective double-blinded clinical trial, oral administration of nilvadipine at 4 mg/day, a DHP calcium-channel blocker, was found to significantly retard the visual field progression in normal tension glaucoma patients over 3 years, while significantly increasing the choroidal and optic nerve blood flow by about 35%. 9. A multi-instituted prospective double-blinded clinical trial in normal tension glaucoma patients revealed that the rate of MD deterioration under monotherapy with either topical nipradilol or timolol was around -0.05 dB/year, thought to be considerably slower than -0.25 dB/year, the commonly estimated rate of MD deterioration by pressure-independent damaging factors. The current results indicate the possibility of treatment of pressure-independent damaging factors of open-angle glaucoma in Japanese open-angle glaucoma patients with oral nilvadipine and topical anti-glaucoma agents.     

Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma.

The purpose of this study was to determine how a topical carbonic anhydrase inhibitor, dorzolamide, alters visual function and ocular blood flow in persons with normal-tension glaucoma. Eighteen normal tension glaucoma patients, after washout of other ocular medications, were treated for four weeks with 2% dorzolamide, three times daily. A control group of eleven other normal-tension glaucoma patients received placebo eye drops. Patients were studied before treatment, and after two and four weeks of treatment. Each study included assessment of central visual function (contrast sensitivity), intraocular pressure (IOP), and several aspects of ocular hemodynamics, including measures of retinal arteriovenous passage time, retinal arterial and venous diameters, and flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries. Dorzolamide significantly reduced IOP at two and four weeks (each p<0.01), and at the same time increased contrast sensitivity at both three and six cycles per degree (each p<0.05). Neither of these variables changed significantly in the control group. Dorzolamide also accelerated retinal arteriovenous passage time of fluorescein dye, at constant retinal arterial and venous diameters (p<0.05), but failed to change flow velocities in any retrobulbar vessel. The ability of dorzolamide to improve contrast sensitivity in persons with normal-tension glaucoma may be related to either IOP reduction or altered ocular perfusion.     

Efficacy and safety of once-daily levobunolol for glaucoma therapy

We studied the ocular hypotensive efficacy and safety of 0.5% levobunolol hydrochloride and 0.5% timolol maleate administered topically once daily for 3 months in 91 patients (46 in the levobunolol group and 45 in the timolol group) with primary or secondary open-angle glaucoma or ocular hypertension. In this randomized double-masked parallel clinical study, intraocular pressure (IOP) was successfully controlled in 78% of the patients who received levobunolol and 89% of those who received timolol. The overall mean decrease in IOP was 5.6 mm Hg (decrease of 23%) in the levobunolol group and 6.7 mm Hg (26%) in the timolol group, a nonsignificant difference. In both groups the overall mean IOP during treatment was significantly lower than the pretreatment value (p less than 0.001). For both treatment groups changes in heart rate and blood pressure were minimal. We conclude that both 0.5% levobunolol and 0.5% timolol administered once daily are effective and safe in lowering IOP in most patients with ocular hypertension or open-angle glaucoma.     

Midterm Results and the Problems of Nonpenetrating Lamellar Trabeculectomy with Mitomycin C for Japanese Glaucoma Patients

PURPOSE: To present midterm results and problems pertaining to nonpenetrating lamellar trabeculectomy (NPT) with mitomycin C (MMC) for Japanese glaucoma patients. METHODS: Thirty-nine patients (39 eyes) with primary open-angle glaucoma or normal-tension glaucoma underwent NPT. The results were compared with those in patients treated by penetrating trabeculectomy (PT) with MMC. In addition, the NPT patients were classified into two groups (group A, 24 patients treated between April 1998 and April 1999; group B, 21 patients treated from May 1999 onward), and the results were compared. RESULTS: The average intraocular pressure (IOP) was 12.6 +/- 2.8 mmHg with NPT and 12.4 +/- 3.0 mmHg with PT. No statistical differences between NPT and PT were identified with respect to IOP at any time after surgery. A life-table analysis showed that the probability of success (good IOP control) was 37.2% with NPT and 62.5% with PT. No significant difference was detected in postoperative IOP change or in the probability of success between NPT groups A and B. CONCLUSIONS: While postoperative IOP is similar between PT and NPT, the probability of success is better with PT than with NPT. Postoperative laser treatment after NPT is effective but sometimes has a negative influence on IOP control.     

Twenty-four-hour time course of intraocular pressure in healthy and glaucomatous Africans: relation to sleep patterns

OBJECTIVE: The study was performed in early middle-aged African natives with primary open-angle glaucoma to compare the 24-hour intraocular pressure (IOP) variations in healthy versus young glaucoma patients, because IOP follows a circadian (24-hour) oscillation in healthy Caucasians. DESIGN: Case-control study. PARTICIPANTS: Sixteen healthy African volunteers (age 24.5 +/- 1 years, mean +/- standard error of the mean) and 11 open-angle glaucoma African patients (age 36.2 +/- 3.3 years). METHODS: IOP was measured hourly during 24 hours with a Modular One pneumatonometer (Modular One, Digilab, Cambridge, MA), which allows measures in supine subjects. To allow the IOP measurement at night, subjects were awakened under polysomnography (electroencephalogram, electromyogram, electro-oculogram) recorded at night and during a 90-minute afternoon nap. MAIN OUTCOME MEASURES: Hourly IOP values were analyzed for circadian rhythmicity with the Cosinor technique and in relation to the state of wakefulness, light sleep (stages 1 and 2), slow-wave sleep (stages 3 and 4), and rapid eye movement (REM) sleep upon awakening. RESULTS: Sleep patterns did not differ between patients and healthy volunteers. As expected, in the healthy subjects, IOP followed a 24-hour rhythm with a nocturnal peak value (acrophase), and the variations in IOP during sleep were related to sleep structure, being lowest during REM sleep and highest during slow-wave sleep. In the glaucoma patients, however, the 24-hour rhythm of IOP was reversed, with an afternoon acrophase and an early morning trough. CONCLUSIONS: These data suggest a circadian phase shift in IOP in glaucoma patients, with maintained relation to sleep structure.     

Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography

PURPOSE: To compare circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma with subjects with normal eyes. METHODS: Thirty-two patients with normal-tension glaucoma and 32 age-matched normal subjects who had no history of systemic disorders and no currently treated systemic disorders, especially diseases of the autonomic nervous system, were studied. An ambulatory electrocardiogram was installed that recorded heartbeats for 48 hours. Low-frequency and high-frequency values were calculated as markers of the autonomic nervous system status based on heart-rate variability using a power-spectrum analysis. RESULTS: The low-frequency values of patients with normal-tension glaucoma during the spans of an active day and a resting night were significantly greater than those of normal subjects, and this difference was emphasized during the night resting span. However, the high-frequency values of patients with normal-tension glaucoma were similar to those of normal subjects. The normal subjects showed a significant age-related decrease in all investigated parameters except the low-frequency values during the resting span. However, the patients with normal-tension glaucoma showed a significant age-related decrease only in low-frequency values during the active day. Patients with normal-tension glaucoma with progressive visual field defects showed much greater values than other cases, although the values were not significantly different. CONCLUSION: These results indicate that a disturbance of the circadian rhythm of the autonomic nervous system may exist in patients with normal-tension glaucoma.     

0.2%阿法根与0.5%噻吗心安治疗原发性开角型青光眼和高眼压症临床观察

目的 证实0．2％阿法根（Alphagan）滴眼液治疗原发性开角型青光眼和高眼压症的降眼压效果及安全性。方法 选择43例原发性开角型青光眼或高眼压症患者，随机分成Alphagan组和噻吗心安（Timolol）组，2组均每日用药2次，将点第1滴药后1，2，4，6，8周的眼压与用药前的基线眼压进行对比研究，并同时观察心率和血压（收缩压与舒张压）等全身及局部不良反应。结果 每组用药后1，2，4，6，8周平均眼压与用药前平均眼压比较有显著性统计学意义（P＜0．01）；每组用药后各时间点平均眼压比较无统计学意义（P＞0．05）。2组用药前与用药后各时间点比较无统计学意义（P＞0．05）。说明0．2％Alphagan和0．5％Timolol降眼压作用明显，而两种药的降眼压效果无显著性差异。0＝2％Alphagan组无明显与0．5％Timolol每日2次用药比较，降眼压效果显著并相似，但0．2％Alphagan对心率无影响，可作为抗青光眼药物的一种主要选择，特别是对有心血管疾病的患者。