青光眼发病机制,治疗方式

1、Aqueous productionAqueous humour is produced from plasma by the ciliary epithelium of the ciliary body pars plicata, using a combination of active and passive secretion（既有主动分泌也有被动运输）.A high-protein filtrate passes out of fenestrated capillaries (ultrafiltration) into the stroma of the ciliary proces

2、ses, from which active transport of solutes（溶质） occurs across the dual-layered ciliary epithelium. The osmotic gradient thereby established facilitates the passive flow of water into the posterior chamber. Secretion is subject to the influence of the sympathetic nervous system, with opposing actions

3、 mediated by beta-2 receptors (increased secretion) and alpha-2 receptors (decreased secretion)（互相拮抗调节）. Enzymatic action is also critical carbonic anhydrase（碳酸酐酶） is among those playing a key role.1The trabecular meshwork（小梁网） (trabeculum) is a sieve-like（筛状） structure at the angle of the anterior

4、chamber (AC) through which 90% of aqueous humour leaves the eye. It has three components. The uveal meshwork（葡萄网） is the innermost portion, consisting of cord-like（索状） endothelial cell-covered strands arising from the iris（虹膜） and ciliary body stroma. The intertrabecular（小梁） spaces are relatively la

5、rge and offer little resistance to the passage of aqueous.The corneoscleral meshwork lies external to the uveal meshwork to form the thickest portion of the trabeculum. It is composed of layers of connective tissue strands with overlying endothelial-like cells. The intertrabecular spaces are smaller

6、 than those of the uveal meshwork, conferring greater resistance to flow.The juxtacanalicular (cribriform) meshwork is the outer part of the trabeculum, and links the corneoscleral meshwork with the endothelium of the inner wall of the canal of Schlemm. It consists of cells embedded in a dense extra

7、cellular matrix with narrow intercellular spaces, and offers the major proportion of normal resistance to aqueous outflow.The Schlemm canal is a circumferential channel within the perilimbal sclera. The inner wall is lined by irregular spindle-shaped endothelial cells containing infoldings (giant va

8、cuoles) that are thought to convey aqueous via the formation of transcellular pores. The outer wall is lined by smooth flat cells and contains the openings of collector channels, which leave the canal at oblique angles and connect directly or indirectly with episcleral veins. Septa commonly divide t

9、he lumen into 24 channels.1Anatomy of outflow channels: A, Uveal meshwork; B, corneoscleral meshwork; C, Schwalbe line; D, Schlemm canal; E, connector channels; F, longitudinal muscle of the ciliary body; G, scleral spurRoutes of aqueous outflow: A, trabecular; B, uveoscleral; C, irisAqueous Humor D

10、rainage Pathways of Healthy and Glaucomatous EyesSimple intraocular pressure：High intraocular pressure has direct damage to the optic nerve. 2High intraocular pressure directly oppresses optic nerve fibers, blocks axoplasmic transport, thereby damaging retinal ganglion cells. Increased intraocular p

11、ressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons.3, 4Trans-lamina cribrosa pressure difference5Mitochondrial DNA mechanismAbnormally elevated intraocular pressure can directly lead to mtDNA damage and mutation, leading to mitochondrial dysfunction, there

12、by mtDNA further damages and mutates, forming a vicious circle, causing RGC progressive apoptosis. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF).Vascular dysregulation, ra

13、ther than an atherosclerosis, leads to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage.6High concentrations of glutamate causing RGC excitotoxic damage is the main cause of death in glaucom

14、a patients.7 Increased oxidative stress and increased ROS production play an important role in the development of glaucoma.8In recent years, it has been found that the immune system plays an important role in the development of GON.药物治疗的局限性：91. 很多患者仅用药物治疗不能降至理想的目标眼压。2. 药物副作用3. 昂贵的药费4. 长时间用药可能会影响今后的手

15、术效果5. 随着用药时间的延长，降眼压作用减弱6. 可能与全身药物产生交叉反应7. 药物产生的副作用干扰患者生活8. 患者长期用药的依从性差Table 1 Summary of drugs used to treat glaucoma10Drug classMechanismClinical useOcular side effectsSystemic sideeffectsProstaglandin analoguesLatanoprostTravoprostBimatoprostTafluprostIncrease aqueous humor outflowPreferred first-

16、line therapy (lowering of IOP by 67 mm Hg) Superior lowering of IOP; proof of neuroprotection pendingBlurred visionLid changesDry eyesHeterochromiaHypertrichosisHyperemiaUncommonb-blockersTimololBetaxololLevobunololDecrease aqueous humor productionAcceptable first line therapy (lowering of IOP by 56

17、 mm Hg) Proof of neuroprotectionBurning/stingingBroncho-spasmWorsening heartfailureBradycardiaHeart blockDepressiona-agonistsBrimonidineIncrease aqueous humor outflow, decrease aqueous humor productionAppropriate first-line therapy (lowering of IOP by 34 mm Hg) Proof of neuroprotectionHyperemiaAller

18、gicconjunctivitisSomnolence (morecommon inchildren)CarbonicAnhydrase inhibitorsDorzolamideBrinzolamideDecrease aqueous humor productionAppropriate first line therapy (lowering of IOP by 34 mm Hg) No proof of neuroprotectionBurningHyperemiaAllergicconjunctivitisAllergic reactionAngioedema(rare)LASER

19、TREATMENT OF GLAUCOMALaser trabeculoplastySelective laser trabeculoplasty (SLT)Argon laser trabeculoplasty (ALT)Micropulse laser trabeculoplasty (MLT)Laser iridotomyDiode laser cycloablationLaser iridoplastyALT is effective as medical therapy in lowering IOP.The most common adverse eventwas a transi

20、ent increase in IOP. The incidence of this event was 12% for an increase in IOP of .10 mm Hg and 34% for an increase in IOPof.5 mmHg. Other adverse events included a low-grade iritis. Complications Bleeding occurs in around 50% but is usually mild and stops after only a few seconds; persistent bleed

21、ing can be terminated by increasing contact lens pressure. IOP elevation. Usually early and transient but occasionally persistent. Iritis. Especially if excessive laser is applied or post-laser steroid therapy is inadequate, or in darker irides (including those due to prostaglandin derivative treatm

22、ent). Corneal burns may occur if a contact lens is not used or if the AC is shallow; these usually heal very rapidly without sequelae. Cataract. Localized lens opacities occasionally develop at the treatment site; age-related cataract formation may be accelerated by iridotomy.TRABECULECTOMYNON-PENET

23、RATING GLAUCOMA SURGERYDRAINAGE SHUNTS青光眼引流器的应用能减少结膜下和滤过道的瘢痕形成，从而大大提高手术的成功率。目前用于治疗青光眼的房水引流器件有：Ex-press引流钉Ahmed引流阀SOLX Gold Shunt超微青光眼金质分流器IStent小梁网分流微支架Eyepass小梁网分流器T-FLUX引流器AquaFlowTM胶原青光眼引流器FNPT引流器等。9目前治疗青光眼的引流装置，采用被动的工作原理，依靠简单的物理压强进行调节，且不能与眼压监测相结合形成随时精确控制的智能系统，因此治疗的效果也很有限，眼压不可控，微管结构易被堵塞仍是未解难题。目前另

24、一个研究热点是MEMS眼压测试系统，其系统植入眼内，用MEMS压力传感器采集眼压，同时用射频将电能输送到眼内能量接受系统，其电能驱动体内传感器和射频收发系统降眼压发送到体外智能的压力传感与压控引流是两个独立的系统。Complications The rate of serious complications is similar to that of mitomycin trabeculectomy. Excessive drainage, resulting in hypotony and a shallow anterior chamber. Malposition (Fig. 10.46

25、A) may result in endothelial or lenticular touch with corneal decompensation and cataract respectively. Ciliary sulcus or pars plana tube placement can be used in some eyes to negate the possibility of corneal touch. Tube erosion through the sclera and conjunctiva (Fig. 10.46B). Corneal decompensati

26、on due to endothelial cell loss. Double vision due to extraocular muscle interference; this may be a higher risk with some implants than others. Early drainage failure may occur as a result of blockage of the end of the tube by vitreous, blood or iris (Fig. 10.46C). Late drainage failure occurs in a

27、bout 10% of cases per year and is comparable to, or perhaps slightly better than, that following trabeculectomy.11. Bowling, B., Kanski's Clinical Ophthalmology. Elsevier Saunders, 2016.2. 黄春玲, 青光眼视神经损伤发病机制的研究进展. 右江民族医学院学报, 2014. 36(01): p. 97-99.3. Morrison, J.C., et al., Understanding mechanisms of pressure-induced optic nerve damage. Prog Retin Eye Res, 2005. 24(2): p. 217-40.4. Golzan, S.M., A. Avolio, and S.L. Graham, Hemodynamic interactio