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【文摘发布】激素性青光眼研究进展

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一篇关于激素性青光眼的翻译，欢迎感兴趣的战友校对！

Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature
皮质类固醇诱导性高眼压和青光眼——文献进展简要综述
Relief Jones III and Douglas J. Rhee

Purpose of review
目的
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.
本文简要综述了激素诱导的高眼压和青光眼的研究进展，包括其危险因素、病理生理学机制以及治疗方案的选择。并且有关玻璃体腔内注射曲安奈德引起青光眼的文献也被重点回顾。
Recent findings
最新进展
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.
原发性开角型青光眼、可疑青光眼患者以及青光眼家族史都是使用激素后眼压反应性升高的危险因素。最近的研究提示，年龄较轻可能是玻璃体内应用激素的患者眼压升高的危险因素。眼压升高的机制被认为是由于小梁网细胞外基质的沉积引起的房水流出阻力增加。
Summary
总结
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.
人们认识激素性高眼压和青光眼已经50多年了。了解其危险因素、发病特点以及病理生理学机制有助于临床医师去预防、监测和治疗激素性高眼压和青光眼。
Keywords
关键词
intravitreal triamcinolone, ocular hypertension, review,
steroid-induced glaucoma
玻璃体内氟羟泼尼松龙，高眼压，综述，激素性青光眼

Curr Opin Ophthalmol 17:163–167. # 2006 Lippincott Williams & Wilkins.
Harvard Medical School, Department of Ophthalmology, Massachusetts Eye and
Ear Infirmary, Glaucoma Service, Boston, Massachusetts, USA
Correspondence to: Douglas J. Rhee MD, Assistant Professor of Ophthalmology,
Harvard Medical School, Department of Ophthalmology, Massachusetts Eye and
Ear Infirmary, Glaucoma Service, 243 Charles Street, Boston, MA 02114, USA
Tel.: +617573 3670, Fax: +617573 3707; e-mail: dougrhee@aol.com
Current Opinion in Ophthalmology 2006, 17:163–167
Abbreviations
ECM extracellular matrix
IOP intraocular pressure
IVTA intravitreal triamcinolone acetonide
POAG primary open-angle glaucoma
# 2006 Lippincott Williams & Wilkins
1040-8738

Introduction
引言
Increased intraocular pressure (IOP) can occur as a consequence of oral, intravenous, inhaled, topical, periocular, or intravitreal corticosteroid therapy . If the ocular hypertension is of a significant magnitude, not recognized, and not treated, subsequent glaucomatous optic neuropathy can develop (that is, steroid-induced glaucoma).
口服、静脉注射、吸入、局部应用、球周或玻璃体内应用皮质类固醇药物均可引起眼内压的升高[1–6,7•,8••, 9–11]。如果眼内压的升高达到显著的程度，而没有被发现并给于治疗的话，就会出现青光眼的视神经损害（即类固醇性青光眼）。
Steroid-induced ocular hypertension was first reported in 1950 when McLean [12] reported an increase in IOP associated with the systemic administration of adrenocorticotrophic hormone (ACTH). The first report of increased IOP caused by the local administration of cortisone occurred four years later [12]. Since those initial reports, corticosteroidinduced glaucoma has been studied intensively. A number of predisposing risk factors have been identified [14–23,24••]. The intraocular potency and mode of administration have been shown to be important in initiating an ocular hypertensive response [1–6,7•,8••,9,25]. Recently, the popular use of intravitreal triamcinolone acetonide (IVTA) for subretinal fluid, macular edema, and adjunctive therapy in the treatment of choroidal neovascularization has led to an increased incidence of corticosteroid-induced ocular hypertension from IVTA [7•,8••,9,26–28,29•].
类固醇诱导性高眼压最早在1950年由McLean [12] 报道，他当时报道了一例由于全身应用促肾上腺皮质激素(ACTH)而导致了眼内压的升高。在4年之后，有人报道了第一例由于局部使用可的松而致眼压升高患者[12]。从此之后，人们对类固醇性青光眼进行了大量研究，确定了多种主要的危险因素[14–23,24••]。激素的眼内活性和给药方式在诱发高眼压反应中起重要作用[1–6,7•,8••,9,25]。最近，玻璃体内注射曲安奈德的疗法被广泛应用于视网膜下积液、黄斑水肿以及脉络膜新生血管的辅助治疗，这导致了玻璃体内注射曲安奈德所致眼压升高患者的增加[7•,8••,9,26–28,29•]。
The molecular biological factors contributing to increased IOP are beginning to be better understood and these findings may lead to additional management options in the future [30–41]. We will review selected studies with an emphasis on glaucoma elevations associated with IVTA.
激素引起眼内压升的高分子机制正在被逐渐了解，这些新的发现在将来可能会产生新的治疗方法[30–41]。本文将重点综述玻璃体内注射曲安奈德所致青光眼的研究进展。

Predisposing risk factors for corticosteroid-induced glaucoma
皮质类固醇诱发性青光眼主要危险因素

When treated with topical steroids for 4–6 weeks, 5% of the population demonstrates a rise in IOP greater than 16 mmHg and 30% have a rise of 6–15 mmHg[10,11]. Several variables have been identified as predisposing risk factors for steroid-induced ocular hypertension. Patients with predisposing risk factors should be followed more diligently when receiving corticosteroids.
局部应用类固醇4-6周，5%的患者眼内压升高超过16 mmHg，30%的患者眼内压升高6–15 mmHg[10,11]。一些因素已经被确认为类固醇诱导性高眼压的主要危险因素。具备危险因素的患者在使用类固醇时应该更经常复诊。
Primary open-angle glaucoma (POAG) patients and glaucoma suspects were shown to be at an increased risk for elevated IOP after treatment with corticosteroids. Studies by Armaly [14,15] revealed that approximately one-third of glaucoma suspects and more than 90% of POAG patients responded with an IOP elevation greater than 6 mmHg after receiving a 4-week course of topical dexamethasone 0.1%. The effect was noted to be more prominent in the eyes of older adult patients compared with the eyes of younger adult patients.
原发性开角型青光眼(POAG)患者和可疑青光眼患者使用类固醇后眼压升高的危险性增加。Armaly [14,15]等人的研究发现在局部应用0.1%的地塞米松4周后，大约1/3的可疑青光眼患者和超过90%的POAG患者眼内压升高超过6 mmHg。这种影响在老年患者比年轻成年人更加显著。
A study by Becker and Mills [16] also indicated that patients with pre-existing glaucoma and glaucoma suspects demonstrated large, highly significant increases in IOP in 2? weeks with the use of topical betamethasone 0.1% and exhibited decreased outflow facility during the treatment period. The IOP returned to baseline or normal in approximately 1 week with discontinuation of steroid treatment. Moreover, other studies showed that simply having a first-degree relative with POAG could make one susceptible to being a steroid-responder [18,19]
Mills [16]等人的研究也发现：既往有青光眼或者可疑青光眼患者在局部使用0.1%倍他米松2周后眼压升高更加显著，而且在治疗过程中表现出房水流畅系数的下降。在停用类固醇药物后大约一周，患者眼内压下降到正常或原来水平。此外，其他研究显示即便是POAG患者的一级亲属也可能是对类固醇高反应的个体[18,19]。
Although older patients are at increased risk, the frequency of steroid responsiveness with age may occur in a bimodal distribution. Children as a group have been shown to be greater steroid-responders as compared with adults. A recent study by Lam et al. [24晻] showed that 71.2 and 59.2% of children receiving topical dexamethasone 0.1% (four times per day and two times per day, respectively) responded with an IOP rise greater than 21 mmHg. Additionally, 36.4 and 21.1% of those same two groups had an IOP rise greater than 30 mmHg. Among children under 6 years old who received dexamethasone 0.1% four times per day, the peak IOP was greater, the net increase in IOP was greater, and the time required to obtain the peak IOP was less. Children greater than 6 years old (children up to age 10 were included in the study) had a similar net increase in IOP, but did not show a significant difference in peak IOP or the time required to reach the peak IOP.
尽管年龄增大会使发病风险增加，但是类固醇敏感患者的年龄分布会呈现出双峰分布。研究显示儿童人群发病率高于成年人。Lam[24晻]等人进行的最近的研究发现局部应用0.1%地塞米松4次/天或2次/天，分别有72%和59%的儿童眼压升高到了21 mmHg以上，而其中36.4%和21.1%的儿童眼压升高到了30 mmHg以上。在6岁以下儿童组，给予0.1%地塞米松4次/天，眼压升高峰值更高，升高值更大，达到眼压峰值所需时间更短。6岁以上儿童（本研究包括了10岁以下的儿童）组眼压增加值相似，但是眼压峰值和达峰时间均没有显著性差异。
Gatson et al. [20] showed that patients with connectivetissue disease tend to be steroid-responders. Men with connective-tissue disease tended to be greater responders, although gender is not typically considered a risk factor in people without connective-tissue disease. Additionally, patients with type-1 diabetes mellitus [20] and high myopia [22] have also been shown to be at increased risk to be steroid-responders.
Gatson[20]等人的研究发现患有结缔组织病的患者似乎对类固醇所致眼压升高敏感。尽管性别在没有结缔组织病人群中并不是一个危险因素，但是男性结缔组织病患者似乎对类固醇更加敏感。此外，I型糖尿病[20]和高度近视[22]也被认为是危险因素。
In summary, pre-existing POAG, status as a glaucoma suspect, or a first-degree relative with POAG are important risk factors for corticosteroid-induced ocular hypertension and glaucoma. Age may be a risk factor; increased risk appears to occur in a bimodal distribution peaking first at age 6. As one progresses through adulthood age may not be a factor until late adulthood when the risk again rises. Finally, those with connective-tissue disease, type-1 diabetes mellitus, and high myopia should all be considered high risk, and prudent follow up should be pursued during periods of corticosteroid use.
综上所述，既往POAG患者、可疑青光眼患者或者POAG患者的一级亲属是类固醇性高眼压或青光眼的重要危险因素。年龄也许是危险因素之一，高发人群年龄呈双峰分布，6岁是第一个高发年龄。在成年后年龄就不再是危险因素，直到老年后发病危险再度升高。最后，结缔组织病、I型糖尿病和高度近视也是危险因素，这类患者在使用类固醇药物时必须谨慎随访。

Types of preparations and modes of administration
类固醇药物剂型和给药方式
Corticosteroids have been shown to exert an ocular hypertensive response relative to the intraocular potency of the steroid [25]. Aside from the relative ability to inhibit inflammation, the other main determinant of intraocular potency is chemical structure. Acetates are more lipophilic and penetrate through the cornea better than phosphates, which are relatively hydrophilic. Medrysone 1.0% caused a 1.0 mmHg rise in IOP, while more potent steroids such as prednisolone acetate 1.0% and dexamethasone acetate 0.1% caused a 10 and 22 mmHg rise in IOP, respectively. Corticosteroids have been shown to cause a elevation in IOP through all modes of administration [1?,7?8晻,9]. The rise of IOP usually occurs over a period of weeks if used topically [15,16,25] and years if used systemically [1]. There have been some reports of an elevation of IOP within hours of initiating intensive topical steroid use [42]. The mode of therapy becomes important when considering corticosteroid use in individuals with pre-existing risk factors for an ocular hypertensive response. Some modes of therapy can be discontinued easily, thereby reducing or reversing any untoward effects on IOP. Other modes of therapy, however, such as subtenon抯, periocular, or intravitreal injections, are not as easily reversed if problems are encountered.
皮质激素导致眼内压升高的效应与其眼内活性有关[25]。除了相对的抗炎效应，化学结构是其眼内活性的主要决定因素。醋酸盐亲脂性强，而磷酸盐亲水性强，因此前者更容易穿透角膜。1.0%甲羟松使眼内压升高1.0 mmHg，而活性更强的1.0%强的松龙和醋酸氟美松可分别使眼内压升高10 和22 mmHg。皮质激素通过所有的给药方式均可诱发眼内压的升高[1?,7?8晻,9]。眼内压在局部应用皮质激素后通常在数周内升高[15,16,25]，而全身给药后则在数年后升高[1]。曾经有报道说局部频繁应用类固醇后数小时内可致眼压升高[42]。当存在危险因素的患者需要应用皮质激素的时候，给药途径就变得很重要了。一些给药方式很容易停药，因此可以减少或逆转不希望出现的对眼压的副作用。而另一些给药方式如球结膜下注射、球周注射或玻璃体内注射，当出现问题时就不那么容易逆转了。

Corticosteroid-induced ocular hypertension associated with triamcinolone acetonide
与曲安奈德有关的激素性高眼压
IVTA has become a useful therapy for many conditions including uveitis, veno-occlusive disease, diabetes, and choroidal neovascularization. When given intravenously, triamcinolone acetonide is 35 times more potent as an anti-inflammatory agent than cortisol.
玻璃体内注射曲安奈德是一些疾病如葡萄膜炎、视网膜静脉阻塞性疾病、糖尿病和脉络膜新生血管等的有效治疗方法。曲安奈德经玻璃体内注射后其抗炎活性是可的松的35倍。
As the list of indications and use of IVTA increases, the incidence of corticosteroid-induced glaucoma associated with IVTA will be more common and more likely to be encountered by ophthalmologists.
随着玻璃体内注射曲安奈德适应症的增加，与其相关的类固醇诱导性青光眼的发病率也将增加，眼科专家将更容易遇到这类病例。
In a recent meta-analysis, Jonas found that intravitreal dosages of approximately 20 mg (the dose more commonly used in Europe) are associated with a 41% prevalence of an IOP elevation greater than 21 mmHg [29昡. All but one patient was managed with topical glaucoma medications and medications were no longer needed about 6 months after the injection. The one patient that required surgery underwent trabeculectomy 9 months after injection and fluid aspirations obtained during surgery contained soluble triamcinolone[43]. It was concluded that IVTA may last 9 months or longer and this fact should be considered prior to repeating the injection.
在最近的一项meta分析中，Jonas发现玻璃体内注射约20 mg 曲安奈德（在欧洲常用的剂量）可以使41%的患者眼内压高于21 mmHg [29]。除了一名患者外全部患者使用了局部降眼压药物，而在注射曲安奈德后约6个月就不再需要降眼压药物了。一名患者最终在注射曲安奈德后9个月接受了小梁切除术，在术中抽取的房水中含有氟羟泼尼松龙。因此他们得出了结论认为玻璃体内注射曲安奈德可以持续9个月或更长的时间，而在重复注射之前应该考虑这一情况。
Another study, by Smithen and colleagues [7•], of 89 patients with a mean baseline IOP of 14.9 mmHg analyzed the prevalence of IOP elevation following IVTA injection. All patients had received a 4 mg (the dosage more commonly used in the United States) of IVTA and were followed for 6 months. The mean pressure increase was 8.0 mmHg and 40.4% experienced a pressure elevation of 24 mmHg or higher; the pressure elevation occurred at a mean of 100.6 days. Patients were also stratified into the categories of ‘no history of glaucoma’ and ‘glaucoma patient’. The patients in these two categories were subsequently divided into two additional categories based on their baseline IOP. Patients without a history of glaucoma and a baseline IOP of at least 15 mmHg had a 60% chance of developing a pressure of at least 24 mmHg, whereas those with a baseline IOP less than 15 mmHg had a 22.7% chance of developing an IOP of at least 24 mmHg. Patients with a history of glaucoma had a 50% chance of developing an IOP of at least 24 mmHg. Of these patients, 50% had a baseline IOP of at least 15 mmHg In this series, patients who received multiple IVTA injections did not experience an increased incidence of elevated IOP, and there was no correlation between IOP elevation and the disease process being treated by the injection. All patients who experienced an IOP elevation had their pressure controlled with a mean of one glaucoma medication. Individuals who were already taking one glaucoma medication required an average of one additional medication. No patients in this study required surgical intervention to control their elevated IOP.
另一项由Smithen和他的同事进行的研究观察了一组平均基线眼压为14.9 mmHg的患者眼压升高与玻璃体内注射曲安奈德的关系。所有患者玻璃体内注射4mg(美国常用的剂量)曲安奈德，随访时间6个月。平均的眼压升高值为8.0 mmHg ， 40.4%的患者眼压升高了24 mmHg以上，眼压升高的平均时间为100.6天。所有患者被分为没有青光眼病史的和青光眼患者两类。在这两类中的患者又根据基线眼压值分为两组。基线眼压15 mmHg以上的没有青光眼病史的患者眼压升高至24 mmHg以上的几率为60%，而基线眼压为15 mmHg以下的该组患者为22.7%。 50%以上的有青光眼病史的患者基线眼压值在15 mmHg以上，而这些患者中50%的眼压升高到了24 mmHg以上。在这一系列研究中，多次玻璃体腔内注射曲安奈德的患者其眼压升高并不增加，而且在原发病与眼内压升高之间也没有明显的相关性。所有眼内压升高的患者经过平均一种降眼压药物治疗后其眼压得到控制。那些已经使用一种降眼压药物的患者平均需要另外增加的一种药物。本研究中所有患者都不需要通过手术来控制眼压。
Singh and colleagues [8••] reported a case series of early and rapid increases in IOP following an IVTA injection in three individuals. In all three cases, a significant rise in IOP occurred within 1 week of IVTA for macular edema. All of the individuals required subsequent surgical intervention to control the elevated IOP. A peculiar finding was the presence of a white material in the angle of one individual on gonioscopy, probably from the injection. A common finding was that all three of these patients were pseudophakic, which may have allowed the medication to move into the anterior segment causing physical obstruction of the trabecular meshwork.
Singh和他的同事们[8••]报道了三个在玻璃体内注射曲安奈德后眼压在早期迅速升高的病例。这三例患者均是因黄斑水肿而玻璃体内注射曲安奈德，在注射曲安奈德后一周内眼压显著升高。三例患者均需要手术治疗控制眼压。比较特殊的发现是在其中一例患者在注射曲安奈德后通过房角镜下发现了白色的物质，或许是由于玻璃体内注射曲安奈德引起的。这三例患者的共同点是均为无晶体眼，这使得曲安奈德可以到达眼前节导致小梁网的功能性阻塞。
To prevent these complications, Vedantham [44] suggested that pseudophakic patients and those with prior vitrectomies be followed with greater scrutiny. In addition, he suggested that filtering the triamcinolone and instructing patients to sleep on their backs might prevent this complication.
为了防止这些并发症，Vedantham [44]建议无晶体眼和前段玻切术后的患者应该密切随访。他还提出对曲安奈德进行过滤处理以及嘱患者仰卧位休息或许有利于防止这些并发症。
Most patients with elevated IOP after IVTA are successfully managed with topical glaucoma medications. Traditional glaucoma surgical techniques can successfully control elevated IOP and are generally required in less than 2% of cases. Filtration surgery is not the only option. One group reported vitrectomy with removal of the intraocular triamcinolone acetonide from the vitreous cavity to treat the elevated IOP [45]. This procedure alone was capable of controlling the ocular hypertension and could also be considered as an alternative if traditional glaucoma treatments are not an option or fail to control the IOP.
大多数在玻璃体内注射曲安奈德后眼内压升高的患者均能用药物成功控制。传统的抗青光眼手术能够成功的控制眼压，而只有不到2%的患者需要手术治疗。滤过性手术并不是唯一的选择。一个研究小组报道了通过玻璃体切割术去除眼内的曲安奈德来控制升高的眼压的方法[45]。当传统的抗青光眼手术不适合选用或者无法控制眼压时，可以考虑这种方法。
IVTA appears to be increasingly popular to treat those with visual loss from macular edema; thus the prevalence of its associated corticosteroid-induced ocular hypertension will continue to rise. Clinicians should be aware that an elevated IOP may occur in nearly half of all cases following a single injection of IVTA. After an injection, they should be followed with greater scrutiny. Postinjection examinations should occur 1 day later and approximately 1 week later for high-risk patients. Regular follow-up examinations should continue for greater than 6 months.
玻璃体内注射曲安奈德来治疗黄斑水肿所致的视力下降看起来越来越流行，因此与之相关的类固醇诱导性高眼压的发病率将持续升高。临床医生必须清楚在玻璃体内注射曲安奈德一次后可以导致将近一半的患者眼压升高。在注射之后，患者应该被谨慎随访观察。在高危患者在注射后第一天和大约一周时都应该接受检查。有规律的随访检查应该至少持续6个月以上。
Weinreb et al. [42] showed that, rarely, some patients with a prior history of glaucoma could develop elevated IOP in a matter of hours following topical administration. Examinations should include monitoring of the IOP and gonioscopy for pseudophakes and patients with prior vitrectomies to detect mechanical obstruction of the trabecular meshwork by the medication. If the IOP cannot be managed with the addition of glaucoma medications, subspecialty care from a glaucoma specialist should be sought as some patients may go on to require surgical intervention.
Weinreb [42] 等人发现，一些局部应用类固醇的既往有青光眼病史的患者在点药后数小时内很少观察到眼压的升高。眼科检查应该包括眼压监测以及对无晶体眼和玻璃体切割术受的患者行房角镜检查以发现小梁网被药物颗粒机械性阻塞的情况。如果在增加一种降眼压药物的情况下无法控制眼压，应该建议患者去青光眼专家处就诊，因为有些患者需要手术治疗。

The pathophysiology of corticosteroid-induced ocular hypertension and glaucoma
类固醇性高眼压或青光眼的病理生理学
The mechanism of corticosteroid-induced ocular hypertension is increased aqueous outflow resistance. There are a number of observations that can be simplified into three broad categories: corticosteroids can induce physical and mechanical changes in the microstructure of the trabecular meshwork; cause an increase in the deposition of substances in the trabecular meshwork, thereby causing decreased outflow facility; and inhibit proteases and trabecular meshwork endothelial cell phagocytosis causing a decrease in the breakdown of substances in the trabecular meshwork.
类固醇诱导性高眼压的发生机制是房水流出阻力的增加。这方面的研究很多，研究结果大致可以分为几类：类固醇能够改变小梁网显微结构的生理和机械性改变；能够增加小梁网细胞外基质的沉积，从而降低房水流畅系数；能够抑制蛋白酶和小梁网内皮细胞吞噬功能，从而减少小梁网细胞外基质的降解。
Changes in the microstructure of the trabecular meshwork may cause a decrease in outflow facility and an increase in IOP. Clark and colleagues [30] showed that the actin stress fibers were reorganized into actin networks that resembled geodesic-dome-like polygonal lattices in human trabecular meshwork cells cultured in the presence of dexamethasone. Upon discontinuing dexamethasone, cross-linking of the actin networks was reversible. The effect was thought to be mediated via trabecular meshwork glucocorticoid receptors. In perfu-sion-cultured human eyes, Clark and colleagues [31] found that steroid treatment had similar microstructural changes and was associated with an increased outflow resistance.
小梁网显微结构的改变能够引起房水流畅系数的降低而升高眼压。Clark 和他的同事 [30]发现：在有地塞米松的培养条件下，小梁细胞内的肌动蛋白张力丝重组为类似线-节结构的多角形网格结构。当终止地塞米松的作用后，小梁细胞内的肌动蛋白交联是可逆的。这种效应被认为是通过小梁网的糖皮质激素受体介导的。Clark和他的同事 [31]在灌注培养的人眼球进行的研究中发现了同样的现象，伴随房水流出阻力的增加。
The accumulated extracellular matrix (ECM) has the potential to affect both the paracellular (that is, the flow in-between trabecular meshwork endothelial cells) and transcellular (that is, the flow through pores created within a single and or between two inner wall Schlemm’s canal cells) levels. Corticosteroids also increase the deposition of ECM in the trabecular meshwork leading to decreased outflow facility. A study by Wilson et al. [32] found an increased deposition of ECM material altering the ultrastructure of the juxtacanalicular region. The corticosteroid dexamethasone increases glycosaminoglycan, elastin, and fibronectin production in cultured trabecular meshwork; the glycosaminoglycan deposition increases further with prolonged steroid exposure [33,34].
细胞外基质的累积可以导致细胞外（即小梁网内皮细胞之间）和经细胞（即通过小梁网内皮细胞上或两个Schlemm’s内壁细胞上的微孔）的房水流出阻力。类固醇也能够通过增加细胞外基质的沉积导致房水流畅系数的下降。Wilson 等人 [32]发现了细胞外基质的沉积导致了邻管区小梁网超微结构的变化。地塞米松可以引起培养的小梁细胞分泌葡萄糖胺聚糖、弹力蛋白和纤维连接蛋白的增加；葡萄糖胺聚糖的沉积会随着地塞米松作用时间的延长而增加[33,34]。
Myocilin is a 55 kDa protein that has also been shown to be induced in cultured human trabecular meshwork cells after exposure to dexamethasone for 2–3 weeks [35]. Mutations in myocilin have been shown to be associated with juvenile-onset and adult-onset POAG [36]. Controversy exists as to if myocilin causes an increase or a decrease in outflow facility. In studies of perfused human trabecular meshwork cell cultures, recombinant myocilin decreased outflow facility, while studies of viralmediated transfer of myocilin in trabecular meshwork cells caused an overexpression of myocilin and increased outflow facility [37].
Myocilin是一种55 kDa的蛋白质，已经发现，在地塞米松作用2-3周后可以诱导小梁细胞表达Myocilin。Myocilin基因的变异已经被证实与青少年性青光眼和成年发病的原发性开角型青光眼有关。有关Myocilin是增加还是降低房水流畅系数的问题存在争议。在通过小梁细胞培养灌注进行的实验中，重组Myocilin降低了房水流畅系数，但是在通过病毒转染Myocilin基因到小梁细胞的研究中去发现Myocilin的表达增加了房水流畅系数[37]。
Finally, decreased outflow facility may be caused by reduced degradation of substances in the trabecular meshwork. Levels of tissue plasminogen activator, stromelysin [34], and metalloproteases [38,39] have been shown to decrease in trabecular meshwork cultures treated with dexamethasone. Furthermore, dexamethasone treatment inhibits trabecular meshwork cell arachadonic acid metabolism [40] and reduces the phagocytic properties of the cells [38,41]. Because these cells function to remove debris deposited in the meshwork, reduced functional activity may lead to reduced outflow facility.
最后，小梁网物质降解的减少同样可能引起房水流畅系数的下降。在地塞米松处理过的小梁细胞中组织纤维蛋白溶酶原激活剂、基质降解酶[34]和金属蛋白酶[38,39]水平下降。而且，地塞米松可以抑制小梁细胞花生四烯酸的代谢[40]，从而降低细胞的吞噬功能[38,41]。由于小梁细胞负责去除小梁网沉积的残渣，这些细胞功能的下降可能引起房水流畅系数的下降。

Conclusion
结论
Corticosteroid-induced ocular hypertension and glaucoma has been recognized for more than 50 years. A number of risk factors have been identified for the development of corticosteroid-induced ocular hypertension and glaucoma, including a personal or family history of glaucoma, young children, older adults, type-1 diabetes mellitus, connective-tissue disease, and high myopia. The intraocular potency and mode of administration are also important risk factors. Increasing use of IVTA will probably lead
to a greater probability that ophthalmologists will encounter steroid-induced ocular hypertension and glaucoma. Research into the underlying mechanisms of this pathophysiological process has improved our understanding of the phenomenon and may lead to more efficacious treatment options in the future.
类固醇诱导的高眼压和青光眼已经被认识50多年了。已经发现了多种发生激素性高眼压或青光眼的危险因素，包括个人或家族的青光眼史、年幼的儿童、老年人、I型糖尿病、结缔组织病以及高度近视。眼内活性和给药方式也是重要的危险因素。玻璃体内注射曲安奈德应用的增加可能使眼科专家遇到这类并发症的机会大增。激素性青光眼或高眼压的病理生理机制的研究增加了我们对这一现象的理解，也许在将来能产生更有效的治疗方法。

References and recommended reading .
Papers of particular interest, published within the annual period of review, have
been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (pp. 213–214).
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triamcinolone injection in patients with and without glaucoma. It allows the
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8 Singh IP, Ahmad SI, Yeh D, et al. Early rapid rise in intraocular pressure after
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286–287.
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IOP after intravitreal glucocorticoid injection. Each of the patients in this case
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the importance of close follow-up. This is in stark contrast to most IVTA-associated
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9 Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of
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11 Becker B. Intraocular pressure response to topical corticosteroids. Invest
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12 McLean JM. Use of ACTH and cortisone. Trans Am Ophthalmol Soc 1950;
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13 Francois J. Cortisone et tension oculaire. Ann D’Oculist 1954; 187:805.
14 Armaly MF. Effect of corticosteroids on intraocular pressure and fluid
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15 Armaly MF. Effect of corticosteroids on intraocular pressure and fluid
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16 Becker B, Mills DW. Corticosteroids and intraocular pressure. Arch Ophthalmol
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17 Becker B. Intraocular pressure response to topical corticosteroids. Invest
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18 Becker B, Hahn KA. Topical corticosteroids and heredity in primary openangle
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19 Davies TG. Tonographic survey of the close relatives of patients with chronic
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20 Gatson H, Absolon MJ, Thurtle OA, Sattar MA. Steroid responsiveness in
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21 Becker B. Diabetes mellitus and primary open-angle glaucoma. Am J
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24 Lam DSC, Fan DSP, Ng JSK, et al. Ocular hypertensive and anti-inflammatory
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Most studies investigating steroid-induced glaucoma examined an elderly patient
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25 Cantrill HL, Palmberg P, Zink HA, et al. Comparison of in vitro potency of
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patients receiving this higher dose of IVTA, IOP elevation was noted about 1–2
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IOP was normalized by topical medications in the vast majority of patients
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本文重点综述玻璃体内注射曲安奈德所致青光眼的研究进展

皮质类固醇诱发性青光眼主要危险因素
1.原发性开角型青光眼(POAG)患者和可疑青光眼患者
2.年龄，类固醇敏感患者的年龄分布会呈现出双峰分布。研究显示儿童人群发病率高于成年人,老年患者发病率也增加。
3.有结缔组织病的患者似乎对类固醇所致眼压升高敏感。尽管性别在没有结缔组织病人群中并不是一个危险因素，但是男性结缔组织病患者似乎对类固醇更加敏感
4.I型糖尿病和高度近视也被认为是危险因素

类固醇药物剂型和给药方式
皮质激素通过所有的给药方式均可诱发眼内压的升高,局部应用后通常在数周内升高，而全身给药后则在数年后升高

类固醇性高眼压或青光眼的病理生理学
类固醇诱导性高眼压的发生机制是房水流出阻力的增加。这方面的研究很多，研究结果大致可以分为几类：类固醇能够改变小梁网显微结构的生理和机械性改变；能够增加小梁网细胞外基质的沉积，从而降低房水流畅系数；能够抑制蛋白酶和小梁网内皮细胞吞噬功能，从而减少小梁网细胞外基质的降解。

与曲安奈德有关的激素性高眼压
Singh和他的同事们发现一例患者在注射曲安奈德后通过房角镜下发现了白色的物质，或许是由于玻璃体内注射曲安奈德引起的。患者为无晶体眼，这使得曲安奈德可以到达眼前节导致小梁网的功能性阻塞。为了防止这些并发症，Vedantham 建议无晶体眼和前段玻切术后的患者应该密切随访。他还提出对曲安奈德进行过滤处理以及嘱患者仰卧位休息或许有利于防止这些并发症。

治疗方法
大多数在玻璃体内注射曲安奈德后眼内压升高的患者均能用药物成功控制。传统的抗青光眼手术能够成功的控制眼压，而只有不到2%的患者需要手术治疗。滤过性手术并不是唯一的选择。一个研究小组报道了通过玻璃体切割术去除眼内的曲安奈德来控制升高的眼压的方法[45]。当传统的抗青光眼手术不适合选用或者无法控制眼压时，可以考虑这种方法。

2007-10-21 10:32