色素性青光眼的发病机制

色素性青光眼是一类发病机制相对"单纯"的继发性开角型青光眼,眼压升高的主要原因在于大量色素颗粒沉积于小梁网并导致房水流出阻力增加.色素颗粒除了机械性堵塞小梁网间隙,还可导致吞噬色素颗粒超负荷的小梁细胞死亡、裂解,小梁柱暴露并相互融合,小梁网间隙变窄甚至消失.此外,葡萄膜巩膜途径房水动力学改变,复杂的分子遗传以及免疫机制...     

Individual factors influencing trabecular morphology in glaucoma patients undergoing filtration surgery

PURPOSE: Epidemiologic studies have shown that various lifestyle characteristics are statistically associated with the chronic open-angle glaucomas. This study was designed to investigate the influence of individual factors on the light-microscopic morphology of the trabecular meshwork in open-angle glaucomas. METHODS: Quantitative computer-assisted topographic analysis of the trabecular meshwork was performed in meridional sections of 80 trabeculectomy specimens from patients with primary open-angle (n = 36), exfoliative (n = 30) and pigment-dispersion (n = 14) glaucoma. Measurements included inner wall length of the, central thickness of the trabecular meshwork, and compactness of the Schlemm canal and trabecular meshwork. Morphologic data were correlated with individual patient data including age, duration of the disease, maximum intraocular pressure, cup-disc ratio, refraction, height, weight, body mass index, a simple morbidity index, previous surgery, and number of topical antiglaucomatous medications used. RESULTS: Inner wall length of the Schlemm canal was significantly lower in eyes with previous filtering surgery (P = 0.03), but not in eyes with a high number of topical medications (P = 0.17). There was a significant tendency for the inner wall length of the Schlemm canal to be shortened in patients where high maximum intraocular pressure was combined with long-term glaucoma (P = 0.027). Body mass index did not differ significantly between patients with primary open-angle, exfoliative, and pigment-dispersion glaucoma and showed no correlation with the quantitative data of the meshwork. The morbidity index correlated well with body mass index (0.0006) and age (P < 0.0001). CONCLUSION: Contrary to findings of experimental mice studies, we found no indication that glaucoma patients with lower body mass index have a larger lumen of the Schlemm canal than patients with a higher body mass index. Although caution should be used when interpreting data from trabeculectomy studies, there is a certain probability that a history of previous filtering surgery and of a long-term high intraocular pressure will be associated with a shortening of the Schlemm canal.     

Argon Laser Trabeculoplasty in the Presurgical Glaucoma Patient

The trabecular meshwork in 334 eyes of 260 patients with medically uncontrolled primary and secondary open-angle glaucoma was treated with the argon laser. The average intraocular pressure reduction obtained was 7.1 mm Hg. Tonographic data showed significant increase in the facility of outflow. Glaucoma surgical intervention was avoided in 87.5% of phakic eyes and in 62.1% of aphakic eyes. Laser trabeculoplasty was found to be effective in primary open-angle glaucoma, pseudoexfoliation glaucoma, pigmentary glaucoma, angle recession glaucoma, glaucoma secondary to uveitis, and in eyes with failed glaucoma surgical procedures. The length of follow-up in this series ranged from one week to 21 months, with an average of five months. The major complication noted was a rise in intraocular pressure following treatment. In one eye, a small central island of vision was lost due to this intraocular pressure elevation. Treating one-half of the angle in each of two treatment sessions separated by a few weeks reduces the degree of this pressure elevation. The glaucoma status of 3% eyes was made worse after treatment with trabeculoplasty.     

Comparative study of argon laser trabeculoplasty in primary open-angle and pseudoexfoliation glaucoma

In 93 phakic eyes--52 eyes with primary open-angle and 41 eyes with exfoliation glaucoma--with increased intraocular pressure, argon laser trabeculoplasty was performed. Fifty to sixty burns were made over 180 degrees of the lower trabecular meshwork. During the follow-up period, visual acuity, intraocular pressure, medication changes and the need for surgery were studied. In 25 eyes a second laser treatment was performed over 180 degrees of the upper trabecular meshwork. Intraocular pressure control was obtained in 81% of the eyes with primary open-angel glaucoma and 71% of the eyes with pseudoexfoliation glaucoma. The average reduction of pressure obtained after laser trabeculoplasty was 9.22 mm Hg for the group of eyes with primary open-angle glaucoma and 13.42 mm Hg for the group of eyes with pseudoexfoliation glaucoma (p less than 0.001). Reduction in medical treatment was obtained in 27 eyes from the 71 eyes with successful reduction of the intraocular pressure. In 6 eyes with successful results after argon laser trabeculoplasty, cataract extraction was performed. The intraocular pressure remained normal in all eyes after the operation.     

Ultrastructural changes in the aqueous outflow apparatus of beagles with inherited glaucoma

Spontaneous glaucoma in the beagle was exhibited after 6 months of age by elevated intraocular pressures and open iridocorneal angles followed by secondary changes. In order to appreciate alterations of the aqueous outflow apparatus in dogs with this autosomal recessive disorder, the eyes of beagles with inherited glaucoma at ages 1 day through 34 months were examined by light, scanning and transmission electron microscopy. Developmentally, no notable differences were observed between normal and preglaucomatous outflow channels through 7 months of age. In 12-month-old glaucomatous chamber angles clustered basement membrane-like material was found scattered throughout the outer corneoscleral trabecular meshwork. In this region elastin-like fibers appeared to be more numerous and arranged less regularly than age-matched normal eyes. Occasional trabecular cells within the corneoscleral trabecular meshwork possessed small clusters of serrated, opaque rods within their cytoplasm. In the older glaucomatous dogs these changes were more generalized and extensive throughout the entire corneoscleral trabecular meshwork. In some individual eyes the anterior chamber angles were observed to be narrow both clinically and histologically. These outflow apparatuses were additionally characterized by compressed, less organized trabeculae with a concomitant build-up of extracellular materials. No correlation was found between the shallowness of the iridocorneal angle and increase in intraocular pressure. Primary glaucoma in the beagle during its earlier phases compared more positively to open-angle glaucoma in man than any of the other spontaneous types in animals.     

Neodymium: YAG laser trabeculopuncture in open-angle glaucoma

Ten eyes of eight patients with open-angle glaucoma (OAG) had neodymium (Nd):YAG trabeculopuncture performed in an investigational protocol as an alternative to surgical intervention. In each, at four to six sites in the mid-trabecular meshwork, three to six superimposed applications were made (2 to 6 mJ). In four of six patients with adult OAG, a small decrease in intraocular pressure (IOP) was noted (from a mean of 25.5 to 20.0 mmHg after 3-4 weeks in the treated eyes, compared to no change at 21 mmHg in the fellow eyes). There appeared to be further attenuation of this IOP effect over the subsequent 2 to 11 months, and all patients demonstrated gonioscopic closure of all the puncture sites with time. One patient demonstrated an acute IOP elevation to 58 mmHg after the procedure, necessitating emergency filtration surgery. In contrast, in four eyes of two patients with juvenile open angle glaucoma, a dramatic lowering of IOP and improvement in tonographic outflow facility was demonstrated, although the effects were only temporary in one patient. YAG laser treatment to the trabecular meshwork may have its greatest potential usefulness when abnormalities in the uveal meshwork are involved, such as in certain cases of juvenile or congenital glaucoma, and may help identify the need for a surgical goniotomy. With more usual forms of OAG, however, widespread use of this technique should be avoided until greater efficacy can be achieved.     

LASER TRABECULOPLASTY: EARLY EXPERIENCE WITH A NEW PROCEDURE

Twenty-live laser trabeculoplasty procedures were performed on 20 patients. All patients were treated as inpatients so that early changes in intraocular pressure could be monitored. The range of fall was recorded: in four cases there was a significant rise in intraocular pressure in the first four hours which, if sustained, could have lead to a further visual field loss in patients with advanced chronic simple open-angle glaucoma. Patients with a high initial intraocular pressure had the greatest fall in intraocular pressure. Those patients with a more pigmented trabecular meshwork with wide open angles were the easiest to treat and gave the best signs of effective laser endpoint reaction. Gonioplasty was performed in many patients with narrow angles, which gave much better access to the posterior trabecular meshwork.     

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.     

Beta-adrenergic blocker therapy and the trabecular meshwork

PURPOSE: To determine whether beta-adrenergic blocker (beta-blocker) therapy for glaucoma causes changes in the trabecular meshwork due to underperfusion. METHODS: Thirty-five eyes from 19 donors with primary open-angle glaucoma (POAG) were divided into three groups: eyes receiving beta-blocker therapy along with standard medications, eyes receiving standard medications but no beta-blockers, and eyes with elevated intraocular pressure but receiving no therapy. Transmission electron microscopy was used to assess the extracellular material of the cribriform region, the structure of the trabecular lamellae, and pigmentation of the trabecular cells. Six eyes from four normal donors were used as controls. RESULTS: No specific changes in the trabecular meshwork were found in eyes receiving beta-blocker therapy. The amount and composition of the extracellular matrix of the cribriform region and the morphology of the lamellae were similar among the three groups of eyes with POAG. Pigmentation of trabecular cells appeared to be a marker for aqueous flow, as significantly more cells contained pigment in regions of the meshwork with thin or normal lamellae than in regions with thickened and fused lamellae. These regions were variable around the circumference of the eye, and were similar between eyes with and without beta-Blocker therapy. CONCLUSION: beta-Blocker therapy could not be proven to cause underperfusion changes in the trabecular meshwork or other discernible effects. Preferential pathways for aqueous flow probably exist within regions of the trabecular meshwork, as evidenced by lamellar appearance and pigmentation of the adjacent trabecular cells.     

Relevance of the pseudoexfoliation syndrome for the glaucomas

Secondary chronic open-angle glaucoma associated with pseudoexfoliation (PEX) syndrome accounts for approximately 25% of all glaucomas and represents the most common identifiable cause of glaucoma overall. The underlying disorder, PEX syndrome, is a generalized process of the extracellular matrix characterized by production and progressive accumulation of an abnormal extracellular material in many intra- and extraocular tissues. Recent data support the pathogenetic concept of PEX syndrome as a type of elastosis affecting particularly elastic microfibrils. Active involvement of the trabecular meshwork in this characteristic matrix process may lead to glaucoma development in 40-60% of the patients. In addition, PEX syndrome also represents an important risk factor for a broad spectrum of spontaneous or intra- and postoperative ocular complications as well as for systemic cardiovascular diseases. PEX-associated open-angle glaucoma represents a relatively severe and progressive type of glaucoma with a generally poor prognosis due to high intraocular pressure levels and fluctuations in the diurnal pressure curve. The primary cause of chronic pressure elevation appears to be local production of PEX material by trabecular meshwork cells and Schlemm's canal cells with subsequent degenerative changes of Schlemm's canal and juxtacanalicular tissues. Additional pathogenetic factors contributing to pressure increase include pronounced melanin dispersion, increased protein concentrations of the aqueous humor, vascular factors, and connective tissue alterations of the lamina cribrosa. Other types of glaucoma, such as acute open-angle glaucoma, provoked by melanin showers during diagnostic mydriasis, or secondary angle closure glaucoma due to pupillary or ciliary block, are also common in PEX patients. The pathogenetic factors TGF-beta1 and TIMP-1/2 appear to be causally involved in this fibrotic process and thus may represent potential targets for specific, rational therapeutic approaches.     

激素性青光眼的研究进展

目的自激素性青光眼首次报道以来已有50多年,人们对于激素性青光眼的危险因素、发病机制和防治都有了进一步的了解。原发性开角型青光眼患者及其亲属,高度近视眼患者等对激素治疗引起的眼压增高较敏感。糖皮质激素主要是通过糖皮质激素受体发挥作用,使小梁网的细胞外基质沉积,增加房水流出阻力而导致眼压升高。进一步了解激素性青光眼的危险因素和发病机制可以有助于我们更好的预防和治疗激素性青光眼。     

小梁网细胞氧化应激在青光眼发病中的研究进展

青光眼是一种常见的不可逆性致盲眼病,病理性眼压升高为主要临床特征。眼压的形成与房水循环密切相关,房水动力学异常,会引起病理性眼压升高。小梁网是房水外流通道的主要组成部分,对维持正常眼压起到非常关键的作用。氧化应激是导致青光眼眼压升高的直接危险因素,表现为氧化与抗氧化作用的失衡。小梁网细胞氧化应激可能导致细胞外基质的沉积与退行性变,使细胞发生自噬和衰老,造成小梁网细胞功能障碍,最终导致房水外流阻力增大,引起病理性眼压升高。本文将针对小梁网细胞氧化应激与青光眼关系的研究进展进行综述,以期为进一步的临床研究提供依据,为探讨青光眼的发病机制、预防及治疗青光眼提供参考。     

氧化应激对小梁网的损伤

青光跟是一组以视网膜神经节细胞(RGCs)丢失和视野缺损为特征的神经退行性疾病,其病理机制尚不完全清楚,眼压升高被认为是青光眼发生和发展最主要的危险因素.小梁网及Schlemm管是房水引流系统的主要组成部分,其结构或功能异常可引起房水流出的受阻进而引起眼压升高.越来越多的证据表明,氧化损伤可能在人小梁网细胞凋亡、功能障碍及其他退行性改变过程中发挥作用.氧化损伤是体内氧化和抗氧化失衡,从而引起脂质过氧化反应、蛋白质变性、DNA损伤等一系列组织病理损伤的过程.既往研究发现青光眼患者房水中氧化应激标志物水平升高,且氧化应激可引起小梁网细胞DNA氧化损伤、细胞内线粒体氧化损伤和炎症反应.本文就氧化应激在小梁网功能损伤中发挥的作用及可能的机制进行综述.     

Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature

PURPOSE OF REVIEW: The purpose of this article is to briefly review the literature of corticosteroid-induced ocular hypertension and glaucoma, its risk factors, the pathophysiology, and treatment options. In particular, literature pertaining to glaucoma in response to intravitreal triamcinolone acetonide will be reviewed. RECENT FINDINGS: Primary open-angle glaucoma, status as a glaucoma suspect, and a family history of glaucoma are risk factors for an ocular hypertensive response with the use of corticosteroid therapy. Recent studies suggest that younger age may also be a risk factor in patients treated via the intravitreal route with corticosteroids. The mechanism of elevated intraocular pressure is increased aqueous outflow resistance owing to an accumulation of extracellular matrix material in the trabecular meshwork. SUMMARY: Corticosteroid-induced ocular hypertension and glaucoma has been recognized for more than 50 years. Knowing the risk factors, prevalence, and pathophysiology can help the clinician prevent, monitor, and treat corticosteroid-induced ocular hypertension and glaucoma.     

Glaucoma with the oculocerebrorenal syndrome of Lowe

PURPOSE: To further describe the glaucoma with the oculocerebrorenal syndrome of Lowe (OCRL) including the responsible filtration angle abnormalities and response to treatment. METHODS: The scientific literature regarding the glaucoma associated with OCRL from 1952, when the first report of the syndrome appeared, to the present was reviewed. The medical records of 7 patients with OCRL were studied. The occurrence of glaucoma, corneal changes secondary to glaucoma, gonioscopic abnormalities, iris features, and response to glaucoma surgery were recorded. RESULTS: Signs of glaucoma are defining abnormalities leading to recognition of OCRL. The OCRL medical literature reports the frequency of glaucoma, secondary clinical signs of increased intraocular pressure (IOP), and results of glaucoma surgery, but little information related to the responsible filtration angle abnormalities. Glaucoma was present in 71% (5 of 7) of patients studied, and was recognized in infancy in 9 of their 10 eyes. Gonioscopy was performed in 6 OCRL patients and revealed the constant presence of open angles, primary filtration angle anomalies, and defects considered secondary to previous infantile lens extractions. The observed anomalies were anterior insertion of the iris, narrowing of the ciliary body band, and decreased visibility of the scleral spur. The angle defects felt to be acquired following lens surgery included a more anterior insertion of the iris on to the trabecular meshwork, pigment dusting of the angle tissues, and iris synechial abnormalities related to the surgery. Bilateral goniotomies were unsuccessful in 4 of 4 patients. The fundi of 6 of 7 patients showed normal optic disc development with variable abnormalities secondary to glaucoma, and normal retinal vessels. Minimal evidence of macular development was observed in a single patient from 1 month of age to his most recent examination at 14 months of age. CONCLUSION: A primary X-linked infantile glaucoma is a defining and frequent component of OCRL and is secondary to expression of a primary filtration angle anomaly. Goniotomy was unsuccessful in all (8) operated eyes. The adverse effects of cataract surgery on the filtration angle structures may influence the results of goniotomy surgery by superimposing a secondary aphakic glaucoma component that may explain the need for alternative glaucoma surgery.     

Transient open-angle glaucoma associated with sickle cell trait: report of 4 cases.

Four black patients, all with sickle trait (SA), developed transient open-angle glaucoma with blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in the fourth no antecedent trauma was described. The intraocular pressure became normal in all 4 cases with the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal.     

What increases outflow resistance in primary open-angle glaucoma?

Intraocular pressure, the most critical risk factor for primary open-angle glaucoma is generated in the trabecular meshwork outflow pathways, which provide resistance to aqueous humor outflow. The resistance is increased in primary open-angle glaucoma, and changes in the quality and amount of the extracellular matrix in the juxtacanalicular region of the trabecular meshwork appear to be causatively involved. The extracellular matrix changes are very likely under control of transforming growth factor-beta2 (TGF-beta2), which is found at high concentrations in the aqueous humor of patients with primary open-angle glaucoma. Additional factors are thrombospondin-1, which activates TGF-beta2 in vivo, and connective tissue growth factor, which is an important downstream mediator of the effects of TGF-beta2 on trabecular meshwork extracellular matrix turnover. In contrast, bone morphogenetic protein-7 (BMP-7) strongly antagonizes fibrogenic actions of TGF-beta2 on human trabecular meshwork cells, indicating that a pharmacological modulation of BMP-7 signalling might be a promising strategy to treat primary open-angle glaucoma.     

Argon laser trabeculoplasty in simple glaucoma

In June 1984 the authors started a prospective study on the treatment of open-angle glaucoma with argon laser trabeculoplasty. The technique used was to treat 180 degrees of the anterior nonpigmented part of the trabecular meshwork with 80 to 100 burns. For retreatment the posterior pigmented part of the trabecular meshwork was coagulated with 80 to 100 burns. The burns were always applied to the pretreated half of the meshwork. At present the study includes 47 eyes treated posteriorly. Of these cases 12 eyes required retreatment. Five eyes had previously undergone an unsuccessful trabeculectomy. The preliminary results are satisfactory. The average reduction in intraocular pressure was 5.9 mm Hg; the mean intraocular pressure before therapy was 23 mm Hg. In 8 cases the trabeculoplasty failed, making a fistulating procedure necessary. The treatment was always well tolerated and there were only minor side effects which never led to any lasting damage.     

Recent developments in understanding the pathophysiology of elevated intraocular pressure

PURPOSE OF REVIEW: The state of the actin cytoskeleton and adhesions of trabecular meshwork cells are important determinants of fluid outflow through the trabecular meshwork. Dysregulation of these subcellular structures or cell loss itself, is expected to adversely affect aqueous humour dynamics and intraocular pressure. This article reviews recent research into the regulation of the cytoskeleton and cell adhesions within the trabecular meshwork. RECENT FINDINGS: Key cytoskeleton regulatory pathways in trabecular meshwork cells and their extracellular matrix significantly influence outflow facility. Integrins and matrix proteins play an important part in cell-matrix communication and mediate trabecular meshwork cytoskeletal changes. Increased cross-linking of the actin cytoskeleton may render the trabecular meshwork stiffer and more resistant to aqueous outflow. In-vitro studies show that transforming growth factor-beta induces actin stress fibres in trabecular meshwork cells, indicating that the cells become more contractile. Myocilin and the heparin II domain of fibronectin also influence the actin cytoskeleton. Mutated myocilin appears to affect trabecular meshwork cells differently from wild-type myocilin and can reduce cell survival. Reduced cell survival is also associated with primary open angle glaucoma, ageing, cellular senescence and oxidative insults. SUMMARY: These findings represent advances in understanding physiological and pathogenic mechanisms within the trabecular meshwork that are relevant to intraocular pressure regulation in health and glaucoma. They pave the way for future research on the pathogenesis of glaucoma and new targets for glaucoma therapy.