青光眼药物治疗的进展

随着人们对青光眼治疗机制研究的深入,涌现了不少新的抗青光眼药物。最经典的治疗方法仍然是降低眼压。新的降眼压药物可能通过以下途径发挥作用：①诱导金属蛋白酶的产生;②使小梁网细胞收缩;③抑制房水的生成;④激活CB-1受体等。另一类重点研究的药物,可增加眼部血流,尤其是视网膜和视神经的血流。对于正常眼压或低眼压性青光眼患,不依赖于眼压改变而增加血流的药物有非常重要的临床意义。神经保护药物,是近年来才出现的新的青光眼治疗方法。虽然其研究历史很短,但包含了多种类型的药物。其中包括NMDA受体阻断剂,神经营养因子,可诱导的一氧化氮合成酶抑制剂,能抑制细胞调亡的药物,保护性自身免疫治疗,干细胞治疗等等。所有的抗青光眼药物都只能稳定病情,而不能治愈疾病,因此理想的药物应该具有较高的性价比。     

Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma

Several vascular factors, including systemic hypertension (or high blood pressure [HBP]), ocular perfusion pressure, and nocturnal hypotension, have been identified as risk factors for the development and progression of glaucoma. The results of epidemiologic studies of these factors and their relationships to intraocular pressure (IOP) and open-angle glaucoma (OAG) have been contradictory. Inconsistent definitions of HBP and OAG, inconsistent design, and differing population characteristics within these studies have obfuscated definitive conclusions. Here, we review the relationships among blood pressure, IOP, and OAG.     

Technical Note: How many readings are required for an acceptable accuracy in pulsatile ocular blood flow assessment?

PURPOSE: Pulsatile ocular blood flow (POBF) assessment aids the diagnosis of ocular diseases with defective ocular haemodynamics, such as glaucoma. Although each successful POBF measure given by the instrument represents five 'repeatable' pulses, there has been no study verifying how repeatable they are. There is also no report on the minimal number of measurements for an acceptable accuracy. METHODS: Forty-three healthy young subjects were recruited and each subject had five consecutive POBF measurements obtained from one randomly selected eye. The coefficient of variation was calculated from the raw data of the five 'repeatable' pulses. The average from five consecutive measurements was considered as the standard for comparison with the first, average of the first two, the first three and the first four measurements. The 95% limits of agreement were determined using the Bland and Altman approach. RESULTS: The coefficient of variation was greater than the manufacturer's claim of within 10%. The mean (+/-S.D.) POBF calculated from five consecutive measures was 732.5 +/- 243.2 microL min(-1). The mean (+/-S.D.) difference between the standard POBF and the first, average of the first two, the first three and the first four measurements was (in microL min(-1)): 12.5 +/- 59.8, 7.8 +/- 42.1, 9.6 +/- 32.5 and 3.7 +/- 19.6 respectively. The corresponding 95% limits of agreement were (in microL min(-1)): +/-117.2, +/-82.6, +/-63.8 and +/-38.4 respectively. CONCLUSIONS: As the five 'repeatable' pulses were not as repeatable as the manufacturer claims, practitioners should not rely on one single POBF measure. An average of three consecutive measurements will be adequate to detect the minimum reported difference in POBF between glaucoma and normal patients.     

细胞骨架作用剂抗青光眼的研究进展

细胞骨架与细胞的各种活动和功能密切相关。在细胞外基质的参与下，细胞骨架调控着房水流出通道的解剖学构架，从而影响小梁网的滤过功能。研究表明，细胞骨架作用剂，如利尿酸、latrunculins、细胞松弛素、某些蛋白激酶抑制剂（H-7、HA1077、Y-27632）、blebbistatin、他汀类药物和BDM均可增加房水流出易度。目前的研究正在致力于探讨细胞骨架作用剂调节房水流出的机制。种种迹象表明，细胞骨架作用剂有可能成为有潜力的抗青光眼药物。     

Clinical outcomes of patterned laser trabeculoplasty as adjuvant therapy in open angle glaucoma and ocular hypertension

AIM: To assess the efficacy and safety of patterned laser trabeculoplasty (PLT) as an adjunctive treatment in open angle glaucoma (OAG) or ocular hypertension (OHT) patients who were under antiglaucoma medical treatment. METHODS: This study was a retrospective review of primary or secondary OAG patients and OHT patients with medically uncontrolled (≥18 mm Hg) intraocular pressure (IOP) who underwent 360o PLT from June 2016 to August 2016. Follow-up visits at week 1, and 1, 3 and 6mo were performed. IOP, best corrected visual acuity (BCVA), complications and eye drop glaucoma medication were recorded at each follow-up visit. Success was defined as IOP reduction ≥20% from baseline. RESULTS: Forty-one eyes of 25 patients were included in this study. Pre-treatment mean IOP was 20.2±1.6 mm Hg. After PLT, IOP was 19.3±5.2, 16.1±2.7, 17.1±3.7 and 16.3±3.5 mm Hg, at 1wk, 1, 3 and 6mo, respectively. IOP reduction from baseline was statistically significant from the first month, remaining stable at 6mo (P<0.001). PLT success at 6mo of follow-up was 48.78%. The number of glaucoma medication per eye (P=0.10) and the mean BCVA both remained constant (P=0.37). Complications included transient IOP spikes in 4 eyes (9.8%) and peripheral anterior synechiae in 7 eyes (17.1%). CONCLUSION: PLT is an effective and safe method for the management of patients with OHT or OAG as an adjunctive therapy. Additional larger studies should be designed to verify the long-term stability of IOP reduction with this laser technology.     

青光眼手术技术的进展

手术是治疗青光眼的主要方法,为了减少术后并发症,提高手术效果,近年来出现了多种新型的手术方式。减少房水生成的手术已从传统的经巩膜睫状体光凝术改进到内窥镜下激光睫状体光凝术。就外引流手术而言,代表性的手术是传统的小梁切除术,近来出现了诸如Ex-Press微型引流钉植入术,Fugo刀经睫状体滤过术等新型手术。而内引流手术包括准分子激光小梁切开术、iStent植入术、内路小梁切开术、Schlemm管成形术以及金质微型引流器植入术。现将青光眼手术治疗进展做一综述。     

Clinical clues of vascular dysregulation and its association with glaucoma

Vascular dysregulation is a condition in which blood flow is not properly distributed to meet the demands of different tissues and could lead to overperfusion or underperfusion. Vascular dysregulation can be primary (occurring alone) or secondary (associated with other disorders, usually autoimmune diseases), and is caused by an imbalance between vasodilator and vasoconstrictor substances produced mainly locally by the vascular endothelium. In most circumstances of vascular dysregulation, the level of endothelin-1 is increased, leading to vasospasm. Vascular dysregulation is present in at least some subgroups of patients with glaucoma, and in these individuals it might have some important therapeutic consequences. In this article we review the evidence linking vascular dysregulation and glaucoma, and evaluate the clinical characteristics that might suggest the presence of vascular dysregulation in the glaucoma patient.     

同步监测青光眼患者24h眼压与血压的意义

青光眼是世界范围内致盲和引起视力损害的主要眼病,也是不可逆性致盲性眼病之一.眼压是青光眼发生发展的重要危险因素,但除眼压外,血压在青光眼进展引起的影响也不可忽视.眼灌注压是血压和眼压的差值,可调节视神经的血液供应.眼压、血压、灌注压在青光眼发生发展中有一定相关性.本文通过对眼压和血压在青光眼中的影响以及24 h眼压和血...     

The role of blood pressure in glaucoma

Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow; however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.     

Alteration in ocular blood flow and its effect on the progression of glaucoma

青光眼是由多种因素引起的神经退行性疾病,眼压过高会损害视神经而导致永久性视力丧失。虽然青光眼的基本病理生理机制尚未确定,但眼组织如视神经,视网膜,脉络膜以及虹膜的血流改变是青光眼发病的重要危险因素。由于不同因素所引发的视神经损害的有限认知,测量方法和治疗方面缺乏,人们对青光眼的理解存在障碍。尽管研究人员在不断地积累证据,力证眼血流的变化在青光眼发病机制中起着重要的作用,但大部分情况下,对于眼血流的变化和青光眼的患病风险之间的关系,他们都持有多样甚至矛盾的结论。本文中,我们回顾了青光眼的不同方面以及眼血流在疾病发展中的影响。     

青光眼药物治疗的回顾和展望

青光眼在全世界范围内是一个主要的致盲眼病.高眼压是多数青光眼主要的危险,也是抗青光眼药物治疗的重点.随着人们对青光眼发病机制的研究以及药理学知识和技术的发展,抗青光眼药物也有了很大进展.现就目前正在使用的抗青光眼药物做一综述性回顾并介绍正在研究开发的抗青光眼新药的药效及降眼压机制.     

Evaluation of Corvis ST tonometer with the updated software in glaucoma practice

AIM: To evaluate the agreement of biomechanically corrected intraocular pressure (b-IOP) and central corneal thickness (CCT) measurements obtained with the updated Corvis ST tonometer versus Goldmann applanation tonometry (GAT) and optical-based corneal pachymetry (OB-CCT) in controls, patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG). Additionally, we examined the differences in corneal deformation parameters provided by the updated Corvis ST among the three groups. METHODS: For each participant, GAT IOP, OB-CCT and measurements with a Corvis ST with updated software were obtained. Bland-Altman analysis was used to assess the agreement between the two measurement methods. RESULTS: A consecutive series of 80 eyes from 80 participants (30 with POAG, 25 with OHT and 25 normal controls) were included in this prospective study. The mean GAT IOP of all eyes was 17.2±3.6 mm Hg, and the mean b-IOP was 15.9±3.7 mm Hg (Spearman’s rho=0.767, P<0.001). The 95% limits of agreement (LoAs) ranged from -3.1 mm Hg to 5.5 mm Hg for GAT IOP and b-IOP. b-IOP was not correlated with OB-CCT (Spearman’s rho=-0.13 P=0.917). Meanwhile there was a weak positive corelation between OB-CCT and GAT IOP–b-IOP difference (Spearman’s rho=0.378, P=0.001). The mean OB-CCT was 549.5±36.4 µm, and the Corvis-CCT was 556.1±41.5 µm (Spearman’s rho=0.900, P<0.001). No statistically significant difference in the new indices provided by the updated Corvis ST was detected among the three groups. Compared with control eyes, POAG eyes had a significantly reduced applanation time 2 after adjusting for OB-CCT and GAT IOP (P=0.048). CONCLUSION: Corvis b-IOP and CCT correlate well with GAT IOP and OB-CCT. b-IOP is not affected by CCT, which might be an advantage, especially in thick or thin corneas. Corvis ST yields shorter applanation time 2 measurements in patients with POAG, which might reflect altered corneal viscoelasticity.     

青光眼巩膜瓣下蓄水池样小梁切除术的临床研究

目的评价巩膜瓣下蓄水池样小梁切除术治疗青光眼的效果。方法回顾54例（64眼）青光眼的治疗情况。观察组26例（32眼）采用巩膜瓣下蓄水池样小梁切除术;对照组28例（32眼）采用传统小梁切除术。术后随访6个月,观察比较两组术后眼压、滤过泡及并发症情况。结果术后6个月观察组平均眼压为（16.2±4.2）mmHg,对照组平均眼压为（19.8±6.2）mmHg,（P〈0.01）,观察组功能性滤过泡形成率明显高于对照组（P〈0.01）,并发症发生率低于对照组（P〈0.05）。结论巩膜瓣下蓄水池样小梁切除术降压效果、安全性均优于传统小梁切除术,并发症少,是一种较好的抗青光眼手术方式。     

Mid-term results of patterned laser trabeculoplasty for uncontrolled ocular hypertension and primary open angle glaucoma

AIM: To describe the safety and efficacy of patterned laser trabeculoplasty (PLT) as an adjunctive treatment in primary open angle glaucoma (POAG) and ocular hypertension (OHT) after 18-month follow-up in Hispanic population.METHODS: A single-center, retrospective study was conducted. All patients with OHT or POAG undergoing PLT from June 2016 to August 2016 were included in the study. Investigated parameters were intraocular pressure (IOP), the number of IOP-lowering medications, best corrected visual acuity (BCVA), laser parameters and postoperative adverse events. Primary efficacy outcome measures were the proportion of eyes achieving an IOP reduction ≥20% at 18mo versus baseline medicated IOP or a reduction in the number of medications while maintaining IOP values.RESULTS: From 40 PLT-treated eyes (mean baseline IOP 20.3±1.7 mm Hg), 24 patients were analyzed (age 63.4±7.3y). The mean IOP reductions from baseline across visits (months 1, 3, 6, 9, 12, and 18) ranged from 14.1% to 20.8%. Success rate after 18-month follow-up was 61.7% with a mean IOP of 16±3.2 mm Hg (P<0.001). The number of glaucoma IOP-lowering medications per eye (preoperative 2.1±1.1 and postoperative 2.3±1.1, P=0.86) and the mean BCVA (preoperative 0.10±0.22 and postoperative 0.11±0.22 logMAR, P=0.42) remained stable. Adverse events comprised transitory IOP spikes in 4 eyes (10%) and peripheral anterior synechiae in 7 eyes (17.5%).CONCLUSION: Mid-term results of PLT show that this procedure may be an efficacious and safe technique to approach medically uncontrolled OHT or POAG patients.     

Measuring and interpreting ocular blood flow and metabolism in glaucoma

There is a growing body of evidence suggesting that vascular dysfunction is related to several prominent ophthalmic diseases, including glaucoma. The vast majority of studies providing data on ocular circulation and disease pathophysiology use a relatively small number of complicated ocular blood flow imaging techniques. Although these imaging technologies are not commonly used in clinical settings, understanding the medical literature characterizing ocular blood flow requires familiarity with their methodology and function. This review highlights the imaging technologies most commonly used to investigate ocular blood flow, including color Doppler imaging, confocal scanning laser ophthalmoscopic angiography with fluorescein and indocyanine green dye, Canon laser blood flowmetry, scanning laser Doppler flowmetry, and retinal photographic oximetry. Each imaging technique's ability to define vascular function and reveal pathology is discussed as are limitations inherent to each technology. The ultimate goal of this review is to provide the physician with a clinically relevant foundation for differentiating the various ocular blood flow outcome measures often presented in the literature and determine how they are related to ocular health and disease.     

国产与进口拉坦前列素滴眼液降眼压作用的短期效果比较

目的 比较国产与进口拉坦前列素滴眼液的短期降眼压效果。设计 随机、开放、平行对照的临床研究。 研究对象  原发性开角型青光眼患者和高眼压症患者42例。方法 对上述患者按所用药物的不同依随机表法分为A、B两组。A组28例（28眼）,滴用国产拉坦前列素滴眼液（特力洁）,B组14例（14眼）,滴用进口拉坦前列素滴眼液（适利达）,均为每日1次,每次1滴,共28天。受试者于入组当日及用药后第28天8:00、11:00、14:00、16:00测眼压,第7、14、21天则于8:00测眼压。眼压测量采用Goldmann压平眼压计,测量3次取平均值。裂隙灯显微镜观察角膜、虹膜、晶状体情况。主要指标  眼压值。结果 A组用药前眼压为（23.99±1.51）mm Hg, 用药后1～4周眼压分别为（18.04±1.27）mm Hg、（17.75±1.43）mm Hg、（17.63±1.50）mm Hg、（17.49±1.47）mm Hg,用药后眼压明显下降,与用药前相比差异有统计学意义（F=105.72,P=0.000）。B组用药前眼压为（24.37±1.55）mm Hg,用药后1～4周眼压分别为（17.91±1.35）mm Hg、（17.71±1.39）mm Hg、（17.55±1.34）mm Hg、（17.44±1.17）mm Hg,与用药前相比,用药后眼压明显下降,差异有统计学意义（F=67.85 P=0.000）。A、B两组用药前眼压比较无显著性差异（P=0.43）,用药后1～4周两组眼压比较无显著性差异（P值分别为0.76、0.93、0.86、0.89）。入组当日8:00、11:00、14:00、16:00  A、B两组眼压之间的比较无显著性差异（P值分别为0.46、0.44、0.50、0.31）,用药后28天8:00、11:00、14:00、16:00  A、B两组眼压之间的比较无显著性差异（P值分别为0.89、0.85、0.94、0.98）。用药28天时两组患者角膜、虹膜、晶状体均无异常改变。结论  本文的小样本、短期研究显示,国产拉坦前列素与进口拉坦前列素均能有效降低原发性开角型青光眼及高眼压症患者的眼压,两者之间的降眼压效果无显著差异。（眼科, 2012, 21: 111-114）     

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.     

Green tea—a new perspective of glaucoma prevention

AIMTo determine how green tea and catechins can affect intraocular pressure (IOP) changes.METHODSTotally 43 young volunteers were included in the study. The experiment was held between noon and 2 p.m. Two extracts—green tea and epigallocatechin gallate (EGCG, 400 mg capsules) and placebo (400 mg capsules) were used in the study. Participants were divided into three groups. Green tea extract group (GT group) had 17 subjects, EGCG extract group 17 subjects, control (placebo) group 9 subjects. IOP was measured with the Icare tonometer before and 30min, 1, 1.5, 2h after the consumption of each extract and placebo. Results were analyzed using the IBM SPSS program. Statistical confidence level P<0.05.RESULTSThe most significant reduction of IOP from the beginning of the experiment was measured after 2h in GT group (left 2.18±3.19 mm Hg, P=0.012; right 2.59±1.97 mm Hg, P<0.000) and after 1h in EGCG extract group (left 2.41±2.98 mm Hg, P<0.004; right 1.94±1.98 mm Hg, P<0.001). In control group no significant changes were measured.CONCLUSIONPeople who have increased IOP or risk factors for glaucoma development, could benefit from drinking green tea or its concentrated extracts in moderate doses.