Medikamentöse Glaukomtherapie

The prospective multicenter randomized controlled clinical trials (RCTs) Ocular Hypertension Glaucoma Treatment Study (OHTS), Early Manifest Glaucoma Trial (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CITGS) and Collaborative Normal Tension Glaucoma Study (CNGTS) are often named as landmarks for glaucoma management as the results of these studies provided the evidence for numerous therapeutic decisions in clinical practice. The studies confirmed the consensus that reduction of intraocular pressure reduces the risk of glaucoma progression covering the whole spectrum of glaucoma from ocular hypertension to advanced glaucoma. Furthermore, the identification of new risk factors allows a higher precision of assessment of the risk of progression. The RCTs achieved the main goal of high level of evidence, thus making progress in the understanding of glaucoma and its treatment and bridging consensus-based and evidence-based decisions. However, the implementation of the results into clinical practice needs adequate and accurate interpretation of the results.     

青光眼视野损害的评价方法

青光眼是眼科常见的不可逆性致盲眼病,其主要损害是视网膜神经节细胞（RGCs）及其轴突的变性和丢失,最终可导致视野损害和视力下降。视野检查是青光眼早期诊断以及随访过程中观察病情进展最重要的视功能检查方法,但由于视野检查存在较强的主观性,因此如何建立客观、规范的视野评价和分析方法一直受到青光眼学者们的关注。就目前临床及研究中常用的视野缺损分级方法,包括视野指数、青光眼半视野检测（GHT）、晚期青光眼干预研究（AGIS）评分法、早期青光眼试验（EMGT）评分法、多中心青光眼初始治疗研究（CIGTS）评分法等,及其优缺点进行综述,希望能够对临床及科学研究中视野评价方法的选择有所帮助。     

The European Glaucoma Prevention Study and the Ocular Hypertension Treatment Study: why do two studies have different results?

PURPOSE OF REVIEW: To understand the results of the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study and to explain differences in their findings and recommendations. RECENT FINDINGS: The value of lowering intraocular pressure with medical therapy to delay or prevent the progression from ocular hypertension to primary open-angle glaucoma has been the subject of two recently completed large clinical trials, the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study. In the Ocular Hypertension Treatment Study, patients were randomized to either medical treatment to achieve a 20% reduction in intraocular pressure or to careful observation. European Glaucoma Prevention Study patients were randomized to receive either topical dorzolamide or the vehicle for the commercially available solution without a specific intraocular pressure goal. The apparent difference in benefit of reducing the conversion rate by lowering intraocular pressure in these two studies may be explained by understanding the methodological differences in study design. SUMMARY: The benefit of lowering intraocular pressure to reduce the rate of progression from ocular hypertension to primary open-angle glaucoma has been established in the Ocular Hypertension Treatment Study. Failure to demonstrate a comparable benefit in the European Glaucoma Prevention Study relates to the selective drop-out of treated and untreated patients with higher intraocular pressure levels and to the failure to achieve sufficient lowering of intraocular pressure. The evidence that the placebo effect was responsible for progressive intraocular pressure-lowering over the 5-year study is not convincing and is likely a result of the regression to the mean phenomenon.     

Update on prospective glaucoma intervention studies

BACKGROUND: Previously published prospective therapeutic intervention studies in ocular hypertension and glaucoma are summarized. MATERIAL AND METHODS: The concept of intraocular pressure reduction was evaluated in normal tension glaucoma ["Early manifest glaucoma trial (EMGT)"], the "Collaborative normal-tension glaucoma study (CNTGS)" and ocular hypertension ["Ocular hypertensive study (OHTS)" as well as the "European glaucoma prevention study (EGPS)"]. Early open angle glaucoma patients were included in the EMGT trial as well as the "Collaborative initial glaucoma treatment study (CIGTS)", whereas advanced glaucoma patients were examined in the "Advanced glaucoma intervention study (AGIS)". RESULTS: The study design, the results and the conclusions will be highlighted in the text. CONCLUSIONS: The therapeutic concept of intraocular pressure reduction decreases the risk of progression by 50 % in normal tension glaucoma, ocular hypertension and early open angle glaucoma. The mean pressure reduction to 12 mmHg in advanced glaucoma abolished visual field progression. The natural course of the disease documented by the control groups is now known. Sensitive glaucoma progression detection is clinically available by glaucoma change probability maps (Humphrey-full threshold perimetry) used in the EMGT.     

Normal-tension Glaucoma Management: A Survey of Glaucoma Sub-specialists in Korea

PurposeTo investigate the current management patterns of glaucoma subspecialists with regard to normal-tension glaucoma (NTG) in Korea and to determine the effect of the two largest NTG trials on their clinical practice.MethodsA questionnaire survey was sent to glaucoma subspecialist members of the Korean Glaucoma Society. The questionnaire concerned regular practice with respect to NTG and the extent to which it has been influenced by the Collaborative Normal-tension Glaucoma Study and the Low-pressure Glaucoma Treatment Study (LoGTS).ResultsA total of 134 glaucoma subspecialists completed the survey, with a response rate of 56%. The survey reported that 88% and 78% of glaucoma subspecialists were familiar with the Collaborative Normal-tension Glaucoma Study and the LoGTS, respectively. With respect to mild or moderate NTG, most of the respondents (87%–91%) tended to treat their patients immediately without waiting for structural or functional progression. Among the respondents, 47 indicated that the LoGTS results—according to which, 20% of the respondents tended to use brimonidine more often—affected their management. The first-choice topical drugs for NTG were prostaglandin analogues (76%), brimonidine (9%), beta-blockers (8%), and topical carbonic anhydrase inhibitor (6%).ConclusionsRegarding mild-to-moderate NTG, Korean glaucoma subspecialists tended to initiate treatment without waiting for further progression. The impact of the LoGTS on NTG management was not dominant in clinical practice in Korea. Prostaglandin analogs are the most frequently selected first-choice drugs for the management of NTG in Korea.     

Argumente f��r eine prophylaktische Therapie der okul?ren Hypertension

Increased intraocular pressure is currently the only manipulable risk factor for glaucoma. In ocular hypertension the intraocular pressure is increased but the optic nerve head and visual field are thought to show no damage. Classification into glaucoma by means of the optic nerve head is often possible only over a period of time because there is a large overlap between the already pathological and still normal findings. In the Ocular Hypertension Treatment Study (OHTS) the effectiveness of prophylactic treatment was demonstrated. In the OHTS and the European Glaucoma Prevention Study (EGPS) risk factors have been identified, such as increased intraocular pressure, size of the excavation of the optic nerve head, decreased central corneal thickness, increased pattern standard deviation in the visual field and age. Before treatment of ocular hypertension is initiated these risk factors and the patient's personal situation should be considered. The higher the intraocular pressure, the smaller the central corneal thickness and the larger the excavation of the optic nerve and the younger the patient, the earlier treatment should be started.     

Correlation of visual field with quality-of-life measures at diagnosis in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

PURPOSE: To examine the relationship between various clinical measures of visual field and patient-reported measures of symptoms and health status in a large cohort of patients with glaucoma at the time of diagnosis. PATIENTS AND METHODS: The 607 patients in the Collaborative Initial Glaucoma Treatment Study received standardized examinations of visual field at enrollment. In addition, they completed a telephone-administered, health-related quality-of-life questionnaire, which included the Visual Activities Questionnaire (VAQ) and a symptom and health problem checklist. RESULTS: The Visual Activities Questionnaire total and subscale scores, particularly the peripheral vision subscale, correlated weakly but significantly with global visual field scores. Symptoms attributed to glaucoma also correlated weakly but significantly to visual field scores. Correlations with other visual field measures, including only central and pericentral test locations in the scores, did not strengthen the association, and simulating binocular visual field scores produced only slightly stronger correlations. CONCLUSIONS: At diagnosis, most patients were relatively free of glaucoma-related impairments. Various visual field measures derived from clinical visual field test data were only modestly associated with patients' perceptions of health-related quality of life. As the Collaborative Initial Glaucoma Treatment Study population is followed up longitudinally, it will be important to see whether these pertinent associations become stronger.     

The natural history of untreated ocular hypertension and glaucoma

Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful in slowing disease progression, little is known about the natural history of untreated glaucoma. This knowledge can be valuable in guiding management decisions in the era of personalized medicine. A systematic search was performed in Medline (PubMed), Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRIMSA) guidelines. The rate of structural and/or functional progression and conversion to glaucoma or to a more advanced stage of glaucoma are discussed for ocular hypertension and different types of open-angle glaucoma. Forty-three studies were included. Different rates of progression were found both among and within the different diagnostic groups that belong to the open-angle glaucoma spectrum. The highest rate was found in pseudoexfoliation glaucoma, followed by high tension glaucoma, normal tension glaucoma, and ocular hypertension, in decreasing order. The lowest rate was observed in glaucoma suspects. The known rates of progression provide valuable prognostic information for ophthalmologists and patients. Nonetheless, due to high variability among patients, individual progression cannot be accurately predicted and repeated follow-up examinations are required to estimate individual progression.     

Ocular Hypertension Treatment Study (OHTS) commentary

PURPOSE OF REVIEW: To summarize the major findings of the Ocular Hypertension Treatment Study (OHTS). RECENT FINDINGS: Ocular hypertensive subjects who received topical glaucoma medication experienced conversion to glaucoma at less than half the rate of subjects who were monitored without treatment. Risk factors for converting to glaucoma included older age, higher intraocular pressure, larger cup-disc ratio, higher pattern SD, and thinner central corneal thickness. SUMMARY: The OHTS clearly established that medically treating ocular hypertension is efficacious in delaying or preventing the onset of glaucoma. Further, the results may assist in providing useful guidelines for determining who with ocular hypertension should be offered medical treatment.     

Ergebnisse der „Collaborative Initial Glaucoma Treatment Study“ (CIGTS)

The Collaborative Initial Glaucoma Treatment Study (CIGTS) was initiated to evaluate whether local medical therapy or trabeculectomy is the better initial treatment for patients with newly diagnosed open-angle glaucoma. Visual field progression, intraocular pressure, and visual acuity were to be monitored for a period of 5 years. A total of 607 patients were randomly distributed among the two groups and controlled at 6-month intervals. At the same time the investigators tried to record quality of life using a questionnaire. Both trabeculectomy and medical therapy were able to lower intraocular pressure significantly, whereas trabeculectomy was more effective. The results of the questionnaire showed only minor differences between the two groups. The medically treated patients reported slightly more ocular symptoms than the patients in the trabeculectomy group.     

Glaucoma clinical trials and what they mean for our patients

PURPOSE: To provide a perspective on the several randomized clinical trials in glaucoma, to suggest how their results can be used in clinical practice, and to look to the future of glaucoma therapy. DESIGN: A search and review of the glaucoma clinical trials literature, the glaucoma observational studies literature, and the evidence-based medicine literature. METHODS: Analysis of the significance of glaucoma clinical trials data on patient management along with use of patient data to demonstrate how treatment decisions can be used in the practice setting. RESULTS: Glaucoma clinical trials and observational studies strongly support the need to reduce intraocular pressures (IOP) substantially and to maintain those pressures in patients with advanced glaucoma. Whether this aggressive therapy occurs by medications or by filtering surgery does not seem as important as that the treatment is effective and sustained. However, there is not the same strength of evidence for aggressive treatment or even any treatment for most patients with ocular hypertension and for some cases of early glaucoma. Because about half of the patients with open-angle glaucoma will have IOPs less than 21 mm Hg, these patients need to be detected through careful optic disk and visual field assessment. Once patients are detected and treated appropriately, blindness from open-angle glaucoma is unlikely. CONCLUSIONS: The goal of managing ocular hypertension and glaucoma is not to preserve every ganglion cell, but rather to preserve a patient's visual ability to conduct activities of daily living. Risk factors for damage need to be assessed for individual patients and each patient managed as an individual and not as the "average" patient depicted in the results of clinical trials. In the future, neuroprotective therapy other than IOP reduction will provide another means to control glaucoma damage.     

The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna-Neumarkt Glaucoma Study

PURPOSE: To provide data on the prevalence of ocular hypertension and glaucoma and on the diagnostic validity of tonometry. METHODS: In this cross-sectional, population-based study, 4,927 subjects over 40 years of age were examined. Each subject underwent a complete ocular examination as part of the Egna-Neumarkt Glaucoma Study. These examinations were carried out by trained, quality-controlled ophthalmologists, according to a predetermined standard protocol that included a medical interview, applanation tonometry, computerized perimetry, optic nerve head examination and other ocular measurements. The following data were recorded: mean IOP, prevalence of ocular hypertension, primary open-angle glaucoma and normal tension glaucoma. Sensitivity, specificity and the predictive value of the tonometric test, as well as the distribution of IOP in the different groups were also determined. RESULTS: The overall prevalence of ocular hypertension, hypertensive primary open-angle glaucoma and normal tension glaucoma corresponded to 2.1, 1.4 and 0.6%, respectively. Other types of glaucoma accounted for a further 0.9%. The sensitivity and specificity of the tonometric test in recognizing glaucoma (cut-off between 21 and 22 mm Hg) were, respectively, 80.1 and 97.8%. The predictive values of the positivity and negativity of the test were 52.1 and 99.4%, respectively. CONCLUSIONS: The prevalence of ocular hypertension and glaucoma was similar to that found in several recent epidemiological studies. Tonometry alone is obviously not sufficient to ascertain or to exclude the presence of glaucoma; its diagnostic validity however is high and should never be underestimated. An elevated IOP is the main risk factor for glaucoma, with the degree of risk increasing as the level of IOP increases.     

Infrequent confirmation of visual field progression

OBJECTIVE: To evaluate the effects of the repeatability criteria on the detection of change in visual fields by six progression algorithms used in standard automated perimetry. DESIGN: Retrospective, observational case series PARTICIPANTS: Fifty-one glaucoma patients, each with multiple visual fields performed between May 1990 and December 1998, were included. METHODS: Each patient's set of visual fields were analyzed using the glaucoma change probability, the Early Manifest Glaucoma Trial (EMGT) algorithm, a modified glaucoma change probability score, a modified EMGT score, the Advanced Glaucoma Intervention Study algorithm, and the Collaborative Initial Glaucoma Treatment Study algorithm. MAIN OUTCOME MEASURES: The effects of repeatability on the detection of field change, the level of agreement among algorithms, as well as the number of eyes identified as changed with each algorithm, were assessed. RESULTS: Mean follow-up was 34 months (range, 12-87 months). The average percentage of eyes with change based on three consecutive follow-up fields was 8.2% (4.0%-12.5%). However, of those showing change on the initial follow-up, this change from baseline was observed in subsequent examinations on average in 23% (18%-33%), depending on the algorithm. When change was based on just one field, four of the six algorithms noted a significantly greater number of eyes with change. The algorithms, however, did not differ significantly when confirmation of field change required two versus three consecutive follow-up visual fields. CONCLUSIONS: Although current algorithms may help identify change, there are inconsistencies among them. We found that requiring repeatable change from baseline significantly reduces the number of changed eyes identified with each subsequent follow-up field. Identification and confirmation of change in visual fields plays an important role in helping to identify true glaucoma progression; however, the specific methods to do so have yet to be determined.     

Relationship between central corneal thickness and severity of glaucomatous visual field loss in a primary care population.

BACKGROUND: Although the ability of central corneal thickness (CCT) to predict development of primary open-angle glaucoma has become increasingly well recognized, the ability of CCT to predict severity of glaucoma remains uncertain. This study was designed to expand the available knowledge about the relationship between CCT and glaucoma severity. METHODS: Retrospective identification of all patients with a clinical diagnosis of either primary open angle glaucoma (POAG) or ocular hypertension who were seen from September 2002 through May 2003 at the Albuquerque VA Medical Center eye clinic was completed. Eligible subjects were segregated into no, mild, moderate, or advanced visual field loss groups based on Advanced Glaucoma Intervention Study (AGIS) visual field scoring criteria. Following statistical analyses comparing the visual field groups, the sample was divided into thin, intermediate, and thick CCT groups, and further analysis was performed. RESULTS: Mean CCT was significantly higher in the no field loss group compared with all 3 groups with glaucomatous visual field loss. Mean CCT was not statistically different, however, between the mild, moderate, and advanced visual field loss groups. In linear regression analyses, no significant relationship was found between CCT and severity of visual field loss. CONCLUSIONS: Although CCT was associated strongly with development of POAG-related visual field loss, CCT was not associated with severity of visual field loss in this study. These findings suggest that glaucoma patients with thinner corneas are just as likely to have advanced levels of field loss as glaucoma patients with thicker corneas. Prospective studies are needed to validate these findings.     

The European glaucoma prevention study design and baseline description of the participants

OBJECTIVES: The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma. DESIGN: Randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes < or =0.4). INTERVENTION: Patients were randomized to the treatment with dorzolamide or a placebo. MAIN OUTCOME MEASURES: End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides. RESULTS: One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria. CONCLUSIONS: The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.     

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.     

Special considerations in low-tension glaucoma

Low-pressure (low-tension) glaucoma is reviewed in relation to neuroprotection, that is, the therapeutic strategy to keep neurons living and functionally connected to targets within the brain. Baseline results of the Low-Pressure Glaucoma Treatment Study (LoGTS) are reviewed.     

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.     

Management of ocular hypertension and primary open angle glaucoma

Background : Glaucoma and pcular hypertension are among the most common pathologies encountered in clinical practice. Within the next 20 years, patients with these two problems will increase threefold as the population ages. The growing burden of glaucoma worldwide will also become a significant public health problem. The effective management of glaucoma will require the introduction of new screening strategies and better therapeutic approaches to these disorders. Methods : Our current understanding of the epidemiology of primary open angle glaucoma and ocular hypertension is reviewed. Diagnosis and treatment strategies are discussed in the context of the current best available clinical trial and laboratory data. Results : While few patients with ocular hypertension will require therapy, it is the conventional practice to lower the intraocular pressure by at least one‐third once glaucomatous optic neuropathy is detected. Topical beta‐adrenergic antagonists have been the preferred first‐line therapy for primary open angle glaucoma for the past 20 years, but with the advent of topical prostaglandin analogues and alpha‐2 agonists, the effectiveness of medical therapy has improved significantly. The decision to perform glaucoma filtering surgery or laser trabeculoplasty must be carefully considered and based on the past response to medication, the extent and rate of progression of any visual field loss, and on the life expectancy and wishes of the patient. Conclusion : The treatment of chronic glaucoma is directed at preserving vision and interfering with the quality of life of the patient as little as possible. Many older patients who develop primary open angle glaucoma may have a limited life expectancy and do not require aggressive medical therapy or surgery. Many new medications have become available that permit less frequent dosing with fewer local and systemic side‐effects. In the near future, therapies that address the underlying molecular basis of glaucomatous optic neuropathy might become available and further reduce the risk of glaucoma blindness.     

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.