Primäres Offenwinkelglaukom und Allgemeinerkrankungen

The exact pathomechanism of primary open-angle glaucoma (POAG) is still not completely understood. Besides elevated intraocular pressure, which has been identified as a major risk factor, there is mounting evidence for the involvement of systemic factors in the development of glaucomatous damage. Systemic peculiarities described in POAG include cardiovascular, endocrine, neurodegenerative, and sleep alterations. However, some of the studies available on systemic findings in glaucoma patients are contradictory, making further research necessary to identify the exact role of such disturbances in the pathogenesis of the damage. Another difficulty is that many studies are limited by their small sample size, their retrospective nature, and potential selection bias, thus making data interpretation more difficult. Moreover, it is not always clear whether we are dealing with coincidence or a true association between glaucoma and a particular systemic disease. Nevertheless, there is ample evidence for the involvement of vascular factors such as vascular dysregulation and blood pressure in the pathogenesis of POAG.     

Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma

The etiology of primary open-angle glaucoma (POAG) remains the subject of continuing investigation. Despite the many known risk factors and mechanism of damage, the principal treatment objectives in POAG still consist of reduction of intraocular pressure, which although straightforward in many cases, often leaves the clinician with the question of how far to pursue a sufficiently low pressure to prevent further damage. Other risk factors such as hemodynamic insufficiency due to vascular dysregulation and abnormal blood pressure are often overlooked in the day-to-day practice; their harmful effects for glaucoma are, it seems, more potent at night while the patient sleeps and when clinical investigation is most difficult. Although the status of autonomic nervous system is an important determinant of the systemic hemodynamic parameters, this issue is usually ignored by the clinician in the process of glaucoma diagnosis. Consequently, there is a lack of alternative therapies tailored to address associated systemic risk factors for POAG on a case and chronological basis; this approach could be more effective in preventing the progression and visual loss in selected glaucoma cases.     

High myopia as a risk factor in primary open angle glaucoma

Glaucoma, one of the leading causes of irreversible blindness in the adult population worldwide, is a progressive optic neuropathy. Primary open angle glaucoma (POAG) is the most commonly reported type of glaucoma in population based prevalence studies worldwide. Elevated intraocular pressure is a well-known major risk factor for POAG. In addition, there is growing evidence that other risk factors like age, gender, race, refractive error, heredity and systemic factors may play a role in glaucoma pathogenesis. Many studies found that high myopia has been associated with POAG, however, direct and convincing evidences are still lacking. The aim of this review is to summarize the evidences implicating high myopia as a risk factor in the pathogenesis of POAG.     

Open angle glaucoma. Identification of vascular risk factors

Although the clinical picture of primary open-angle glaucoma (POAG) is well described, the exact mechanism leading to this specific type of damage is still under investigation. Among the vascular risk factors, hypotension and vasospasm seem to have an important role in the pathogenesis of this disease. This review presents the importance of hypotension and vasospasm in the pathogenesis of POAG and an inventary of the principal methods for their detection.     

A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma

Despite intense research, the pathogenesis of primary open-angle glaucoma (POAG) is still not completely understood. There is ample evidence for a pathophysiological role of elevated intraocular pressure; however, several systemic factors may influence onset and progression of the disease. Systemic peculiarities found in POAG include alterations of the cardiovascular system, autonomic nervous system, immune system, as well as endocrinological, psychological, and sleep disturbances. An association between POAG and other neurodegenerative diseases, such as Alzheimer disease and Parkinson disease, has also been described. Furthermore, the diagnosis of glaucoma can affect the patient's quality of life. By highlighting the systemic alterations found in POAG, this review attempts to bring glaucoma into a broader medical context.     

原发性开角型青光眼进展的危险因素研究概况

原发性开角型青光眼(POAG)进展的危险因素包括全身性及眼部因素,眼部因素包括眼压及非眼压因素.在以往的多中心研究中,眼压对于由高眼压症发展为POAG及其在POAG进展中的作用已经明确,而目前降低眼压也是临床惟一有效地延缓、控制青光眼视神经损害进展的主要因素.制定目标眼压,进行降眼压治疗尤其是控制昼夜眼压波动对于阻止青光眼进展非常重要.非眼压危险因素包括高龄、中央角膜厚度增厚、视乳头出血、晶状体囊膜剥脱征、初始的青光眼严重程度及双眼罹患青光眼等.其他因素包括近视、青光眼家族史、眼部低灌注压、低血压、心血管疾病、高血压、高血脂等血管或血液性因素.POAG进展的危险因素研究在一定程度上揭示了POAG的发病机制及临床发病规律,对于指导临床医师决定随诊频率、选择治疗方案及提高治疗效率意义重大.     

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.     

原发性开角型青光眼的系统性危险因素

眼压异常升高是原发性开角型青光眼最主要的危险因素。临床目前一直沿用以眼压为靶点的青光眼诊疗模式。近年来发现,循环血流、体质指数、颅内压、营养代谢、中医偏颇体质类型、某些系统性疾病等多种系统性危险因素可能与青光眼发生、发展和转归相关。纠正系统性危险因素能否延缓青光眼进展被日益关注,成为潜在的青光眼辅助诊疗靶点。本文对各类青光眼系统性危险因素进行介绍,倡导重视系统性危险因素,提出以系统危险因素评估和个性化眼体同治相结合的青光眼诊疗体系。（眼科,2022,31:325-329）     

Primary open-angle glaucoma genes

A substantial fraction of glaucoma has a genetic basis. About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin). Mutations in these genes have a high likelihood of leading to glaucoma and are rarely seen in normal subjects. Other cases of POAG have a more complex genetic basis and are caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. These factors are more frequently detected in patients with POAG, but are also commonly observed in normal subjects. Additional genes that may be important in glaucoma pathogenesis have been investigated using quantitative traits approaches. Such studies have begun to identify genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness. Each of these different approaches to study glaucoma genetics is providing new insights into the pathogenesis of POAG.     

Primary open angle glaucoma and low tension glaucoma--pathogenesis and mechanism of optic nerve damage]

The etiology, pathogenesis and mechanism of optic nerve damage in primary open angle glaucoma (POAG) and low tension glaucoma (LTG) were investigated by experimental glaucoma in monkey and by follow-up studies of many patients over 15 years, by pathohistological and immunohistochemical analysis. 1) LTG was proved to be a real glaucoma, showing pressure-dependent optic nerve damage. The pathological entity was a primary weakness of the lamina cribrosa (LC), and therefore even normal pressure could deform the LC. Due to backward distortion of LC the channels were disarranged and twisted, inducing mechanical optic nerve damage. There was no active vascular damage or vascular constriction at the site of the optic nerve damage. The filling defects of the advanced glaucomatous optic disc were not the cause of optic nerve damage, but the result of regressive vascular change after axon bundle loss. Splinter hemorrhage of the optic disc might be the result of the same process. 2) The weakness of LC might be induced by the abnormal metabolism of the extracellular matrix of the LC. 3) To arrest the progressive optic nerve damage in LTG, the intraocular pressure (IOP) should be maintained under 12, or ideally, 10 mmHg. 4) The optic nerve damage in POAG was not only pressure-dependent, but also dependent on the weakness of the LC, as in the case of LTG. In the early stage the IOP should be under 19 mmHg, in the advanced stage under 14 mmHg in order to arrest progression for over 15 years. 5) In advanced experimental glaucoma of monkeys, the LC showed reduction of elastin, fragmentation of collagen, and change of proteoglycans. 6) As in the LC, the trabecular meshwork also showed abnormal metabolism and abnormal deposits on the extracellular matrix in POAG, and LTG as well. 7) POAG and LTG might belong to the same family in which common abnormal metabolism of LC and trabecular meshwork induce various clinical features.     

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。     

New directions in the treatment of normal tension glaucoma

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.     

Is exfoliation syndrome a sign of systemic vascular disease?

Exfoliation syndrome (ES) is an age‐related disorder in which greyish‐white flakes accumulate in different tissues in the anterior eye. Its pathogenesis is not completely known, but it results in electron‐dense microfibrils. The finding that these can be seen outside the eye in many visceral organs inspired the theory that ES might be a part of a generalized disorder. It was postulated that ES might contribute to increased morbidity, mainly of systemic vascular diseases. This review is a summary of the existing knowledge. The prevalence of arterial hypertension (AHT) in elderly populations is > 30%. No differences have been found in the frequency of AHT among patients with ES or exfoliative glaucoma (EG) compared with those with primary open‐angle glaucoma (POAG) or no ES. There are conflicting reports of frequencies of ischaemic heart disease (IHD). A recent registry‐based study that used uniform criteria for IHD found no difference in the rate of IHD between patients with EG and those with POAG. However, findings of elevated homocysteine levels in the plasma and aqueous humour of patients with ES or EG suggest an increased vascular risk. No studies have yet been conducted to assess possible links between ES and systemic vascular diseases. In a single‐blind study, ES was associated with abdominal aortic aneurysm, but this was not found in a large, cross‐sectional investigation. The frequency of ES in patients with diabetes mellitus (DM) is only about half of that when compared in patients with no ES or with POAG. This finding warrants further studies. Molecular genetics research has found no common denominator for ES and the vascular diseases. There is no evidence that ES or EG are related to increased mortality for cardiovascular diseases. Further large‐scale, randomized clinical studies are required. At present there are no known medical indications that infer an increased systemic vascular risk or imply a need for the complete internal medical examination of a symptom‐free patient with newly diagnosed ES in the eye.     

High prevalence of sleep-disordered breathing in patients with primary open-angle glaucoma

PURPOSE: Elevated intraocular pressure and systemic hemodynamic changes are main risk factors in primary open-angle glaucoma (POAG). Sleep-disordered breathing (SDB) characterized by snoring, excessive daytime sleepiness and insomnia is accompanied by large swings in blood pressure and repetitive hypoxic periods during sleep. The aim of this study was to evaluate whether there is any relationship between SDB and POAG. METHODS: Consecutively, 212 outpatients with POAG and 218 outpatients without POAG were recruited. Both eyes were examined. An interviewer-administered semi-structured questionnaire was used to collect SDB-related symptoms. RESULTS: After controlling for age, relative to control group, POAG patients showed a high prevalence of snoring (47.6%, p=0.04), snoring plus, excessive daytime sleepiness (27.3%, p=0.01) and snoring plus, excessive daytime sleepiness, plus insomnia (14.6%, p=0.01). CONCLUSION: We found a high prevalence of SDB in patients with POAG. Chronic hemodynamic changes and recurrent severe hypoxia resulting from SDB may contribute to anoxic optic nerve damage, implicated in glaucoma.     

正常眼压型青光眼与高眼压型原发性开角型青光眼是否为同一类型疾病

基于临床考虑,在《我国原发性青光眼诊断和治疗专家共识》中,将正常眼压型青光眼与高眼压型原发性开角型青光眼同归类为原发性开角型青光眼,归属于一类疾病的两个亚型,分界点在于眼压是在正常范围还是高于21 mm Hg(1 mm Hg=0.133 kPa)。但是正常眼压型青光眼与高眼压型原发性开角型青光眼是否应属同一类型疾病,眼...     

Vascular risk factors in glaucoma: a review

Glaucoma, one of the major causes of blindness in the world, is a progressive optic neuropathy. Elevated intraocular pressure is a well-known major risk factor for glaucoma. In addition, there is growing evidence that vascular factors may play a role in glaucoma pathogenesis. Systemic (e.g. hypertension, diabetes) and ocular vascular factors (e.g. ocular blood flow, ocular perfusion pressure) have been assessed for associations with glaucoma. However, direct and convincing evidence for primary mechanisms of glaucoma is still lacking. The aim of this review is to summarize the evidence implicating vascular factors in the pathogenesis of glaucoma, with particular emphasis on the role of ocular blood flow and ocular circulation as risk factors for primary open angle glaucoma.     

Metabolic abnormalities in patients with primary open-angle glaucoma

PURPOSE: Although there are few data on the underlying mechanisms of primary open-angle glaucoma (POAG), it has been suggested that metabolic diseases may play a role in the evolution of the disease. We carried out the present study to investigate the involvement of metabolic disturbances in POAG pathogenesis. MATERIAL/METHODS: Serum metabolic parameters were evaluated in 49 POAG patients without a known history of diabetes mellitus and 72 age and sex matched individuals without glaucoma (control group). RESULTS: Among the metabolic parameters examined, only fasting serum glucose and uric acid levels were found significantly higher in patients with glaucoma compared to the control population (117+/-17 mg/dl vs 105+/-11 mg/dl, p=0.05 and 6.2+/-1.9 mg/dl vs 5+/-1.2 mg/dl, p=0.006, respectively). Additionally, a considerably greater proportion of patients had disturbances of the carbohydrate metabolism and hyperuricemia. CONCLUSION: We conclude that disturbances of carbohydrate and uric acid metabolism could play a role in glaucoma damage and pathogenesis.     

Peripheral vasospasm and nocturnal blood pressure dipping--two distinct risk factors for glaucomatous damage?

PURPOSE: To evaluate the relationship between peripheral vasospasm and circadian blood pressure rhythm in patients with primary open angle glaucoma (POAG). METHODS: Nail-fold capillaroscopy, combined with a cold provocation test, and 24-hour blood pressure monitoring was carried out in 130 patients with POAG (M:F 58:72; mean age 60 +/- 14 years), 99 with high-tension glaucoma (HTG) and 31 with normal-tension glaucoma (NTG). Peripheral blood flow parameters were compared for patients with a nocturnal fall in mean systemic blood pressure (MBP) of less than 10% (non-dippers), patients with a nighttime MBP fall of 10-20% (dippers), and patients with a nighttime MBP fall of more than 20% (over-dippers). RESULTS: Patients with POAG showed a significantly lower blood flow velocity both at baseline (p < 0.01) and after cold provocation (p < 0.02) and a significantly higher percentage of cold-induced blood-flow standstill (p < 0.0001) in the nail-fold capillaroscopy than normal controls. The numbers of non-dippers (50), dippers (66) and over-dippers (14) did not differ between the HTG and NTG group. There were no significant differences between non-dippers, dippers, and over-dippers in peripheral blood flow parameters. CONCLUSIONS: Our findings indicate that vasospasm and low blood pressure may be distinct risk factors for glaucomatous damage. It also appears that screening for vascular dysregulation and systemic hypotension should not be restricted to NTG patients alone.     

Systemic high-sensitivity C-reactive protein levels in normal-tension glaucoma and primary open-angle glaucoma

PURPOSE: To determine the systemic high-sensitivity C-reactive protein (hsCRP) level in patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG). MATERIALS AND METHODS: With the exclusion of patients with cardiovascular and other systemic diseases, 40 patients with NTG, 40 with POAG, and 40 normal controls were enrolled in this study. Each patient underwent blood sampling for hsCRP, biochemistry, and lipid profile analysis. RESULTS: Each group had similar demographic parameters including the age, sex, body mass index, heart rate, and blood pressure. There was no statistically significant difference in the hsCRP and biochemistry results between the 3 groups. The lipid profile exhibited a mild elevation in the patients with POAG. CONCLUSIONS: Our data revealed no difference in the hsCRP level between NTG, POAG, and normal controls after exclusion of patients with cardiovascular and other systemic diseases. Systemic vascular inflammation may not be a major cause in the pathogenesis of glaucoma in those without histories of cardiovascular diseases.     

高度近视与原发性开角型青光眼关系的研究进展

临床和实验研究均发现,青光眼患者近视发生率高于非青光眼人群。反之,近视,尤其高度近视（high myopia,HM）人群较其它人群更常伴有青光眼。当HM与原发性开角型青光眼（primary open—angle glaucoma,POAG）并存时,病情变得尤其复杂。两者发病机制之间的关系,目前在分子和基因水平的研究重点是：胶原基因学说和升压基因学说。从病理学角度讲,高度近视与青光眼都是胶原病变;此外,二者的小梁网细胞在糖皮质激素诱导下易表达特异性蛋白,这可能与高度近视、原发性开角型青光眼的TIGR（trabecular meshwork induced glucocorticoid response protein）基因突变有关。本文从流行病学、发病机制、临床特征及诊断注意要点等方面对高度近视与原发性开角型青光眼的关系及研究进展进行综述。