青光眼發(fā)病機制,治療方式

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（既有主動分泌也有被動運輸）.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（溶質(zhì)） 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)（互相拮抗調(diào)節(jié)）. Enzymatic action is also critical carbonic anhydrase（碳酸酐酶） is among those playing a key role.1The trabecular meshwork（小梁網(wǎng)） (trabeculum) is a sieve-like（篩狀） 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（葡萄網(wǎng)） is the innermost portion, consisting of cord-like（索狀） 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.藥物治療的局限性：91. 很多患者僅用藥物治療不能降至理想的目標(biāo)眼壓。2. 藥物副作用3. 昂貴的藥費4. 長時間用藥可能會影響今后的手

15、術(shù)效果5. 隨著用藥時間的延長，降眼壓作用減弱6. 可能與全身藥物產(chǎn)生交叉反應(yīng)7. 藥物產(chǎn)生的副作用干擾患者生活8. 患者長期用藥的依從性差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青光眼引流器的應(yīng)用能減少結(jié)膜下和濾過道的瘢痕形成，從而大大提高手術(shù)的成功率。目前用于治療青光眼的房水引流器件有：Ex-press引流釘Ahmed引流閥SOLX Gold Shunt超微青光眼金質(zhì)分流器IStent小梁網(wǎng)分流微支架Eyepass小梁網(wǎng)分流器T-FLUX引流器AquaFlowTM膠原青光眼引流器FNPT引流器等。9目前治療青光眼的引流裝置，采用被動的工作原理，依靠簡單的物理壓強進(jìn)行調(diào)節(jié)，且不能與眼壓監(jiān)測相結(jié)合形成隨時精確控制的智能系統(tǒng)，因此治療的效果也很有限，眼壓不可控，微管結(jié)構(gòu)易被堵塞仍是未解難題。目前另

24、一個研究熱點是MEMS眼壓測試系統(tǒng)，其系統(tǒng)植入眼內(nèi)，用MEMS壓力傳感器采集眼壓，同時用射頻將電能輸送到眼內(nèi)能量接受系統(tǒng)，其電能驅(qū)動體內(nèi)傳感器和射頻收發(fā)系統(tǒng)降眼壓發(fā)送到體外智能的壓力傳感與壓控引流是兩個獨立的系統(tǒng)。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. 黃春玲, 青光眼視神經(jīng)損傷發(fā)病機制的研究進(jìn)展. 右江民族醫(yī)學(xué)院學(xué)報, 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