Normal-tension glaucoma is associated with sleep apnea syndrome

INTRODUCTION: In normal-tension glaucoma, optic nerve damage occurs without elevated intraocular pressures, hence vascular and pathogenic mechanisms other than intraocular pressure effects have been postulated. However, the exact cause(s) remain unknown. We have looked for an association between normal-tension glaucoma and sleep apnea syndrome, a disease characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of late cardiovascular and neurological sequelae. METHODS: We performed overnight polysomnography in 16 consecutive Caucasian patients with normal-tension glaucoma. The respiratory disturbance index (RDI) during night sleep was used to diagnose and grade obstructive sleep apnea. Patients with an RDI of 10 or more were diagnosed as having obstructive sleep apnea. RESULTS: We observed the following prevalences of obstructive sleep apnea in normal-tension glaucoma patients: 0% (0 of 2) for the group of patients younger than 45 years, 50% (3 of 6) for the age group 45-64 years, and 63% (5 of 8) for the group older than 64 years. Prevalences in the middle and older age group were significantly higher than in a historic control group (p < 0.025 for both, binomial test). CONCLUSION: Normal-tension glaucoma patients constitute a high-risk population for sleep apnea syndrome. Therefore, they should be screened for sleep apnea syndrome, and, if necessary, be treated to avoid late cardiovascular and neurological sequelae.     

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.     

Collaborative normal tension glaucoma study

PURPOSE OF REVIEW: Before this study was done, there was a difference of opinion concerning whether intraocular pressure (IOP) was involved in producing optic nerve damage when there was glaucomatous damage to the optic nerve and characteristic visual field loss, even though the IOP was in the statistically normal range. This article reviews the findings of a collaborative study aimed at finding the answer to this question. RECENT FINDINGS: The level of pressure influences the course of normal tension glaucoma, as evidenced by a slower rate of incident visual field loss in cases with 30% or more lowering of intraocular pressure. The rate of progression without treatment is highly variable, but often slow enough that half of the patients have no progression in 5 years. A faster rate occurs in women, in patients with migraine headaches, and in the presence of disc hemorrhages. Some patients may experience greater benefit from lowering of IOP than others, but further research is needed to be able to identify those most likely to benefit. SUMMARY: As a group, patients with normal tension glaucoma benefit from lowering of IOP. Variable rate of deterioration, as well as lack of progression in a substantial number in 5 years, suggest that treatment should be individualized according to the stage of disease and rate of progression. Traits that help predict risk and rate of progression and response to treatment are beginning to become known and, when fully known, will help guide management decisions.     

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)     

Systemic hypotension: a risk factor for glaucomatous damage?

Four glaucoma patients with rapid progression of visual field damage and excavation of the optic nerve head despite normal or well-controlled intraocular pressure had one factor in common: low systemic blood pressure. Furthermore, when monitored during 24 h, a sustained blood pressure drop during sleep was always observed. Systemic hypotension, therefore, might be a significant risk factor for glaucomatous damage. The authors recommend measuring the blood pressure frequently in such patients, especially at night.     

Bilateral visual field defects with optic disc drusen and secondary open angle glaucoma with PEX--clinical correlation with the HRA

BACKGROUND: Arcuate visual field defects are a typical sign of glaucomatous damage. Elevated intraocular pressure in combination with pseudoexfoliation syndrome (PSX) manifests the diagnosis glaucoma. Beyond this state, in microdiscs with optic disc drusen, the exact classification of the visual field defects is crucial. CASE REPORT: A 57-year-old male with pseudoexfoliation glaucoma was referred because of progressive glaucomatous visual field defects. The visual acuity was right 20/40 and left 20/25. Maximum intraocular pressure was 36 mm Hg. A simple optic nerve atrophy was diagnosed superonasally. The optic disc size was OD 2.24 mm(2) and OS 1.89 mm(2) (HRT I). An Ultrasound B-mode scan demonstrated the diagnosis of optic disc drusen. Over a follow-up of 1 year, a growth tendency was observed, especially in the superonasal quadrant. The mulberry-shaped surface of the drusen was visualized with infrared reflection images (HRA II, 830 nm). Confocal scanning laser ophthalmoscopy (HRA II, excitation 488 nm, 500 nm notch filter) showed an increased intrapapapillary autofluorescence (> 50 % papillary area: OD 1.67 mm(2), OS 1.26 mm(2)). This technique could detect drusen in areas that looked normal in classical retinoscopy. CONCLUSION: The differential diagnosis of arcuate scotomas includes simple optic nerve atrophy and glaucomatous optic nerve atrophy. Optic disc drusen in glaucoma eyes can obscure the main cause of progressive visual field loss. Superficial optic disc drusen can be measured planimetrically over the years. An adequate reduction of intraocular pressure should be realized in these eyes.     

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.     

Optic disc drusen and glaucoma--case report

Optic disc drusen make examination towards glaucoma difficult to interpret. They change nerve head morphology and visual field defects can resembling glaucomatous damage. Patient with strong headache was examined and we found drusen on both optic nerve heads and intraocular pressure about 27 mmHg. Visual fields demonstrated scotomas--in lower half and the enlargement of the blind spot. After topical treatment and intraocular pressure normalization, the patient's complaints had gone. Control examination after one year revealed progression of visual field changes. Electrophysiological examination showed abnormalities typical for glaucoma.     

Nocturnal measurements of intraocular pressure in patients with normal-tension glaucoma and sleep apnea syndrome

BACKGROUND: About half of all normal-tension glaucoma patients and about one third of all primary open-angle glaucoma patients have sleep apnea syndrome. If sleep apnea syndrome causes some cases of glaucoma, the optic nerve damage could result from repetitive nocturnal hypoxias or from repetitive intraocular pressure elevations at the end of the apneas. In this study, we determined the intraocular pressure at the end of long apneas. PATIENTS AND METHODS: In three patients having sleep apnea syndrome and normal-tension glaucoma we recorded in a sleep laboratory during at least six hours of sleep the respiration (oxymetry, nasal and oral air flow, and inductive plethysmography). The intraocular pressure was measured with a pneumatonometer at predetermined times and compared to the values measured at the end of prolonged apneas. RESULTS: The intraocular pressure during normal respiration was in the first patient 19.5 +/- 1.0 mm Hg OD and 19.3 +/- 1.7 mm Hg OS, in the second patient 25.0 +/- 4.2 respectively 25.5 +/- 4.9 mm Hg and in the third one 22 +/- 1.0 respectively 21.3 +/- 1.3 mm Hg. At the end of prolonged apneas the intraocular pressure was in the first patient 19.0 +/- 0.0 mm Hg OD and 19.5 +/- 0.7 mm Hg OS, in the second patient 26.5 +/- 0.6 and 26.8 +/- 0.1 mm Hg and in the third one 20.0 +/- 0.0 respectively 21.0 +/- 0.0 mm Hg. The difference between intraocular pressures during normal respiration and at the end of prolonged apneas was not significant (p > 0.1 for each comparison, paired t-test). CONCLUSIONS: We did not find an increase of intraocular pressure at the end of prolonged apneas compared to periods of normal respiration in patients with sleep apnea syndrome and normal-tension glaucoma. If sleep apnea syndrome causes some cases of glaucoma, it seems more probable that the the optic nerve is damaged by the repetitive hypoxias. Alternatively, an unknown factor might induce both, sleep apnea syndrome and normal-tension glaucoma.     

Predictive factors for progressive optic nerve damage in various types of chronic open-angle glaucoma

PURPOSE: To evaluate whether various types of chronic open-angle glaucoma differ in predictive factors for progression of glaucomatous optic nerve damage. DESIGN: Observational cohort study. METHODS: SETTING: Prospective observational clinical study. PATIENTS: 517 eyes of 300 Caucasian patients with chronic open-angle glaucoma with elevated intraocular pressure (primary open-angle glaucoma, n = 289; secondary open-angle glaucoma, n = 50) and with normal intraocular pressure (n = 178). OBSERVATION PROCEDURE: During follow-up (median: 49 months, 6 months-130 months), all patients underwent repeated evaluation of color stereo optic disk photographs and white-on-white visual field examination. MAIN OUTCOME MEASURES: Progression of glaucoma was defined as neuroretinal rim loss during the study period. RESULTS: For patients with elevated intraocular pressure, significantly predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim, and larger area of beta zone of parapapillary atrophy. In contrast, in the normal intraocular pressure group, a significant predictive factor was presence of disk hemorrhages at baseline. Within the patients with elevated intraocular pressure, the primary open-angle glaucoma group and the secondary open-angle glaucoma group did not differ in predictive factors for progression of glaucoma. CONCLUSIONS: Open-angle glaucoma patients with normal intraocular pressure and open-angle glaucoma patients with elevated intraocular pressure differ in predictive factors for eventual progression of glaucomatous optic nerve damage. It may have clinical importance and may be helpful in the discussion of the pathogenesis of the glaucomas.     

Is neuroprotection a viable therapy for glaucoma?

Treatment of glaucoma continues to be directed at lowering intraocular pressure to decrease the likelihood of disease progression. In the future intraocular pressure reduction might be augmented by other therapeutic approaches. Interest has been increasing in preventing progression of glaucomatous optic neuropathy using approaches based on the premise that glaucoma is a neurodegenerative disease. Neuroprotection of the glaucomatous optic nerve therefore would be an adjuctive therapeutic paradigm for use with conventional intraocular pressure-lowering treatments or by itself.     

Glaucoma and sleep apnea syndrome

Glaucomatous optic neuropathy is multifactorial, with currently one known and modifiable risk factor, with good results on the prognosis and intraocular pressure. Nevertheless, some patients may experience progression of their neuropathy even though their intraocular pressure seems appropriately controlled. Vascular risk factors are hypothesized and researched. Obstructive sleep apnea syndrome (OSAS) could be considered one of these risk factors. Screening for this cardiovascular risk factor in glaucomatous patients presenting evocative signs, should be proposed.     

颅内压与青光眼及其无创测量技术的研究进展

青光眼是世界上第二位致盲性眼病,第一位不可复性致盲性眼病。尽管眼压增高被认为是青光眼性视神经损害的主要危险因素,但是50%的原发性开角型青光眼患者的日常眼压正常,还有一些患者尽管眼压控制良好,但青光眼性视神经损害仍继续发展。这些现象无法用高眼压理论来解释,青光眼患者视神经损害的发病机制仍待探讨。目前国内外的一些研究表明：（1）视神经周围的生物力学的解剖结构包括眼内压,筛板和球后的脑脊液压力在原发性开角型青光眼的发病机制中发挥重要的作用;（2）正常眼压性青光眼患者的脑脊液压力比正常人低,而跨筛板压力差比正常人高;（3）高眼压症患者的脑脊液压力比正常人群高,而跨筛板压力差和正常人之间没有统计学意义。基于以上研究,本文就颅内压与青光眼性视神经损害之间关系的相关研究进展及临床上可行的无创颅内压测量方法作一综述。     

Was bringt die prophylaktische YAG-Iridotomie beim Pigmentdispersionssyndrom?

Despite theoretical considerations concerning the advantage of iridotomy in eyes with pigment dispersion syndrome or early pigment glaucoma, there is a lack of clinical evidence that this procedure has a long-term effect in preventing glaucoma damage under these circumstances. However, several factors may contribute to this lack of evidence, e.g. the statistical problem of a low conversion rate from pigment dispersion syndrome to pigment glaucoma or the inclusion criteria in the studies treating patients older than 40 years or genetic dispositions in pigment glaucoma that are not yet fully clear. On the basis of current data the decision for YAG iridotomy should only be taken in patients younger than 40 years, if the midperipheral iris shows an inverse bowing and the intraocular pressure is normal or slightly increased with no progressive signs of optic nerve damage. In cases of insufficient intraocular pressure and visual defects due to glaucomatous optic nerve damage, incisional glaucoma surgery is usually necessary especially in younger patients with a long life expectancy.     

The case for autoimmunity in glaucoma

Although the majority of patients with glaucoma have elevated intraocular pressure as the presumed etiology for their resultant neuropathy, it is well known that approximately 25% of patients with glaucoma have intraocular pressure within the normal range for their race. These patients may have conditions that facilitate non-pressure related stress to the retina and optic nerve that might directly contribute to their glaucomatous neuropathy and include chronic or intermittent ischemia (i.e atherosclerosis, heart disease, vasospasm, migraine, sleep apnea), altered scleral/optic nerve head morphology that predisposes to glaucomatous stress (i.e myopia); genetic mutations that predispose to glaucoma damage at normal IOP (OPA-1,optineurin, myocilin) and evidence of aberrant immunity that suggests that their glaucoma might be a form of an autoimmune neuropathy (i.e. presumed autoimmune glaucoma). This review provides a critical assessment of the potential role for autoimmunity as an initiating or exacerbating etiology in some patients with glaucoma.     

Okuläres Risiko bei obstruktivem Schlafapnoesyndrom

Purpose

A prospective controlled cohort study examined the effects of obstructive sleep apnea syndrome (OSAS) on the visual field, including morphological and physiological aspects.

Methods

Thirty-two patients with newly discovered and previously untreated moderate to severe OSAS (apnea–hypopnea index >20) were compared with a control group of 32 healthy individuals. Global visual field indices [mean deviation (MD), corrected pattern standard deviation (CPSD)] were compared, and optic disc changes, intraocular pressure, correlations between MD and polysomnography, and the frequency of local defects (using the Humphrey Field Analyzer) were examined.

Results

The MD was significantly reduced (R –1.66/L –1.62 dB; p<0.001) in OSAS patients, whereas there was no difference in CPSD. Diffuse local defects in the middle periphery of the 30° visual field were increased in OSAS patients (p<0.003). Normal intraocular tension values were found in all persons, with no correlation to MD. The incidence of pathological optic disc changes was increased in the apnea group (6.25%).

Conclusions

OSAS seems to lead to reduced sensitivity in the visual field by diffuse rarefaction of nerve tissue in the retina, optic nerve, or both. An increased incidence of development of a low-tension glaucoma is assumed.     

Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma

Fifty-five patients with primary open-angle glaucoma and early glaucomatous damage who had medical therapy and laser trabeculoplasty were followed up for four to 11 years or until progressive glaucomatous damage was documented. Factors associated with the stability or progression of glaucoma were evaluated. Eyes with mean intraocular pressure higher than 21 mm Hg during the follow-up period uniformly had progressive glaucomatous changes. Conversely, eyes with mean intraocular pressure less than 17 mm Hg remained stable, and approximately half of the eyes with mean intraocular pressure between 17 and 21 mm Hg had progressive glaucomatous changes. Patients who remained stable were slightly younger than those with progressive glaucomatous changes (P less than .05), but initial optic nerve head appearance, initial visual field findings, number of medicines used, medical history, and patient gender or race were not statistically associated with stability or progression of the glaucoma. These findings reinforce the importance of intraocular pressure control in primary open-angle glaucoma and the need to identify other markers that help determine the proper level of intraocular pressure for individual patients.     

Empfehlungen notwendiger Kontrolluntersuchungen bei okul?rer Hypertension

Ocular hypertension (OHT) describes a condition with elevated intraocular pressure (IOP) above the norm (?>?21?mmHg). By definition the anterior chamber angle is open and there are neither signs of glaucomatous optic nerve damage nor visual field defects. Thus, for the diagnosis of OHT an extensive baseline examination is mandatory in order to rule out pre-existing glaucomatous damage. Patients with ocular hypertension are at a higher risk of developing glaucoma. Therefore, periodical routine examinations with a standardized protocol for specific follow-up examinations are highly recommended.     

Are large optic nerve heads susceptible to glaucomatous damage at normal intraocular pressure?

To evaluate the effects of the presence of glaucomatous visual field defects and of intraocular pressure elevations on optic nerve head topography, we analyzed 148 left optic nerve heads of 148 patients using laser scanning tomography. The optic discs are classified according to computerized static perimetry and documented IOP readings: 101 discs show normal visual fields (36 normal discs, 22 ocular hypertensives, 28 normotensive glaucoma suspects and 15 ocular hypertensive glaucoma suspects), 47 discs (34 high-pressure glaucoma discs, 13 normal-tension glaucoma discs) demonstrate glaucomatous visual field damage. A two-way analysis of variance discloses significant differences (P<0.01) between the groups of optic discs classified according to perimetry for most topometric parameters evaluated exept for disc area. Classification according to documented IOP (cut off at 21 mmHg) results in larger disc areas in normotensive discs compared to hypertensive optic nerve heads in the study population. Results suggest that large discs may be susceptible to glaucomatous visual field damage at statistically normal IOP readings.This study was supported in part by a grant from the Deutsche Forschungsgemeinschaft DFG Vo 437/1-1 Correspondence to: R.O.W. Burk     

Recommendations for follow-up examinations in patients with ocular hypertension

Ocular hypertension (OHT) describes a condition with elevated intraocular pressure (IOP) above the norm (?>?21 mmHg). By definition the anterior chamber angle is open and there are neither signs of glaucomatous optic nerve damage nor visual field defects. Thus, for the diagnosis of OHT an extensive baseline examination is mandatory in order to rule out pre-existing glaucomatous damage. Patients with ocular hypertension are at a higher risk of developing glaucoma. Therefore, periodical routine examinations with a standardized protocol for specific follow-up examinations are highly recommended.