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Aqueous Humor Karen Gil MD, MHSN Anterior Chamber Angle Structures Located at the internal scleral sulcus (corneoscleral junction) – Trabecular Meshwork – Schlemm’s canal (Both part of the filtration apparatus) – Scleral spur Scleral Spur Lies at the posterior edge of the internal scleral sulcus Pos...

Aqueous Humor Karen Gil MD, MHSN Anterior Chamber Angle Structures Located at the internal scleral sulcus (corneoscleral junction) – Trabecular Meshwork – Schlemm’s canal (Both part of the filtration apparatus) – Scleral spur Scleral Spur Lies at the posterior edge of the internal scleral sulcus Posterior portion the longitudinal ciliary muscle fibers attach Anterior portion many trabecular sheets attach Schematic drawing of the cribriform meshwork and the endothelial lining of Schlemm's canal ( E ). Note the connection between the ciliary muscle tendons ( CM-T ) and the elasticlike fiber plexus, or “cribriform plexus” ( CN ), located mainly in the region between the first and second subendothelial cell layers ( 1. and 2. ). The cribriform plexus is connected to the inner wall endothelium and the plaque material ( P ) by a system of fine fibrils or “connecting fibrils” ( CF ). ( B ) Electron micrograph of a tangential section through the cribriform region almost at the level between the second subendothelial cell layer and the first corneoscleral trabecular lamellas (normal eye). The cells seen in the upper left are subendothelial. The elastic-like fibers of the cribriform region ( arrows ) form a plexus that shows the same equatorial orientation as the network of the elastic-like fibers of the trabecular lamellas. (From Rohen JW, Futa R, LütjenDrecoll E: Invest Ophthalmol Vis Sci 21:574, 1981, reproduced with permission from the Association for Research in Vision and Ophthalmology.) FIGURE 6-2 Drawing of the limbus. Limbal conjunctiva (A) is formed by an epithelium (1) and a loose connective tissue stroma (2). Tenon’s capsule (B) forms a thin, poorly defined connective tissue layer over episclera (C). Limbal stroma occupies the area (D) and is composed of scleral and corneal tissues, which merge in this region. Conjunctival stromal vessels are seen at a; they form peripheral corneal arcades (b), which extend anteriorly to termination of Bowman’s layer (arrow). Episcleral vessels (c) are cut in different planes. Vessels forming intrascleral plexus (d) and deep scleral plexus (e) are shown within limbal stroma. Scleral spur, with its coarse, dense collagen fibers, is shown at f. Anterior part of longitudinal portion of ciliary muscle (g) merges with scleral spur and trabecular meshwork. Lumen of Schlemm’s canal (h) and loose tissues of its wall are clearly seen. Sheets of trabecular meshwork (i) are outer to cords of uveal meshwork (j). An iris process (k) arises from iris surface and joins trabecular meshwork at level of anterior portion of scleral spur. Descemet’s membrane terminates (double arrows) within anterior portion of the triangle, outlining aqueous outflow system. (From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.) A ) Blood supply to the ciliary processes. CCM, Circular ciliary muscle; LCM, longitudinal ciliary muscle; RCM, radial ciliary muscle. ( B ) Vascular architecture in the human ciliary body. 1, Perforating branches of the anterior ciliary arteries; 2, major arterial circle of iris; 3, first vascular territory. The second vascular territory is depicted in 4a, marginal route, and 4b, capillary network in the center of this territory. 5, Third vascular territory; 6 and 7, arterioles to the ciliary muscle; 8, recurrent choroidal arteries. (Modified from Caprioli J: The ciliary epithelia and aqueous humor. In Hart WM [ed]: Adler's physiology of the eye: clinical application, ed 9, St Louis, 1992, Mosby; and Funk R, Rohen JW: Exp Eye Res 51:651, 1990.) Trabecular Meshwork Encircles the circumference of the anterior chamber Occupy most of the inner aspect of the internal scleral sulcus Triangular shape Apex is the Schwalbe’s line (termination of Descemet’s membrane) Base is the scleral spur Trabecular Meshwork Composed of flattened perforated sheets Collagen and elastic fibers embedded in ground substance and covered by basement membrane and endothelium 3-5 sheets at the apex They branch into 15-20 sheets as they extend posteriorly form Schawlbe’s line to the scleral spur Intertrabecular spaces between the sheets connected through pores (“spaces of Fontana”) Trabecular Meshwork Three anatomic divisions: – Uveal meshwork inner sheets attach to the ciliary stroma and longitudinal muscle fibers Cord-like Larger pores – Corneoscleral meshwork outer region attach to the scleral spur Sheet-like – Juxtacanalicular meshwork Connective tissue surrounded by endothelium Fig. 18. Connections of the ciliary muscle (CM) with the trabecular meshwork (TR). Note the different types of muscle tendons (T) connected with the cornea or the elastic-like fiber network of the cribriform layer (EL), which on the other hand is connected with the inner wall endothelium (E) of Schlemm's canal (Sc) by connecting fibrils (CF). SP, scleral spur Canal of Schlemm Circular vessel Considered to be a venous channel (contains AH instead of blood) Lumen lined with endothelial cells joined by zonula occludens Juxtacanalicular Connective Tissue Region separating the endothelial cell lining of the canal of Schlemm from the TM Also called cribriform layer Consist of endothelial cells and fibroblast embedded in al matrix of collagen, elastic-like fibers and ground substance Scanning electron microscope image of the trabecular meshwork, showing multiple stacked collagen and elastin sheets. (AC) Anterior Chamber, (UM) uveal meshwork, (P) large-size pores of the uveal meshwork, (CM) corneoscleral meshwork, (JM) juxtacanalicular meshwork, (SC) Schlemm's canal. Source: Johnson DH and LutjenDrecoll E. Glaucomatous Changes in the Trabecular Meshwork. In: Tombran-Tink J, Barnstable KJ, and Shields MB. Mechanisms of Glaucoma: Disease Processes and Therapeutic Modalities. Totowa, New Jersey: Humana Press, 2008:101. Posterior Chamber Annular area behind the iris Two regions – Canal of Hannover Zonules are located – Canal of Petit Retrozonular space Aqueous Humor Dynamics Produced in the pars plicata of the ciliary body Secreted to the posterior chamber through the non-pigmented ciliary epithelium covering the ciliary processes Passes between the iris and lens and enters the anterior chamber through the pupil Aqueous Humor Flow In the anterior chamber circulates in convection currents Moving down along the cooler cornea and up along the warmer iris Exiting through the periphery of the chamber Aqueous Humor Flow Two exits from the anterior chamber 1. Unconventional outflow: – – – Pass through the spaces within the uveal meshwork (5-35%) Fluid then passes into the connective tissue spaces surrounding the ciliary body muscle bundles, moves into the suprachoroidal space and then is absorbed into and through the sclera Alternately, the fluid is absorbed into the anterior ciliary veins and vortex veins Aqueous Humor Flow 2. Conventional outflow pathway: – The remainder aqueous humor moves through the uveal meshwork and into the narrower pores of the conreoscleral meshwork and trough the juxtacanalicular tissue and the endothelial lining into Schlemm’s canal Aqueous Humor Outflow Conventional outflow pathway – Endothelial cells lining the inner wall of the canal have been found to contain giant vacuoles work as channels of transport – Greatest amount of AH passive diffusion – Depends on the IOP Aqueous Humor Flow Schematic representation of the primate anterior ocular segment. Arrows indicate aqueous humor flow pathways. Aqueous humor is formed by the ciliary processes, enters the posterior chamber, flows through the pupil into the anterior chamber, and exits at the chamber angle via the trabecular and uveoscleral routes. (From Kaufman PL, Wiedman T, Robinson JR: Cholinergics. In Sears ML [ed]: Pharmacology of the eye: handbook of experimental pharmacology, Berlin, 1984, Springer-Verlag. Reproduced with kind permission of Springer Science + Business Media.) Aqueous Humor Outflow Juxtacanalicular tissue contains evaginations that are name internal collector channels (of Sondermann) Endothelial cells lining the external wall of the canal are joined by zonula occludens 25 to 35 external collector channels are distributed around the canal that empty into either the deep scleral plexus or the intraescleral plexus of the veins which drain into the episcleral and conjunctival veins Aqueous veins of Ascher -drain directly to the episcleral veins Fig. 14 Schematic drawing showing the circular course and related vessels of the canal of Schlemm. Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye—An Atlas and Textbook. Philadelphia: WB Saunders, 1971) Venous drainage form the eye Radial episcleral collecting veins – Receive blood form the anterior conjunctiva, limbal arcades, anterior episcleral veins and perforating scleral veins Then they form the anterior ciliary veins (leave the globe anteriorly over the rectus muscles) Venous drainage from the eye – Posteiorly 4 to 7 vortex veins drain the venous system (the choroid, ciliary body and iris) into the superior and inferior ophthalmic veins Venous Drainage form the Eye Blood from the ophthalmic veins drain into the internal jugular vein Descends alongside the internal carotid artery Aqueous Humor Outflow Aqueous Humor Outflow Aqueous Humor Outflow Aqueous humor carries away waste products of the lens and cornea IOP must be kept at a level that is not detrimental to ocular tissue IOP is maintained within a small range by the complex equilibrium between the rate of production and the rate of exit Aqueous Humor Outflow Production remains fairly constant Most cases of increased IOP are caused by decreased aqueous outflow There is greater variability in the amount exiting via the conventional pathway Aqueous Humor Outflow There is normally little resistance to aqueous passage through the sheets of the trabecular meshwork, unless pigment or debris has accumulated within the pores Schlemm’s canal is wide open it also provides little to no resistance to outflow Aqueous Humor Outflow The location of higher resistance to aqueous movement seems to be in the juxtacanalicular tissue (JCT) and the endothelium of the inner wall of Schlemm’s canal 75% of the outflow resistance is at the JCT and 25% at Schlemm’s canal Plaque-like material that accumulates in the extracellular matrix of the juxtacanalicular area either directly or indirectly increases resistance in the outflow pathway Aqueous Humor Outflow Its important that the amount of aqueous formed is equal to the amount that exits the eye Homeostatic mechanisms normally preserve this balance Small variations in either the production or the exit can cause significant changes in IOP Most cases of increased IOP are caused by decrease aqueous outflow – Conventional – Non-conventional Episcleral veins pressure = 8-10mmHg Resistance of the conventional aqueous drainage = 3-4 mmHg/μl/min Average of IOP 15.5 + 2.6 mmHg Aqueous Humor Flow Morning is higher than at night 3.0 μl /min 2.4 μl /min at the afternoon 1.5 μl /min at night Research studies: – 2.4+ 0.6 μl /min Factors Affecting IOP Diabetes – Neovascularization from proliferative diabetic retinopathy can occlude the angle Uveitis – Inflammatory cells and peripheral anterior synechiae can occlude the angle impeding the outflow or cause acute angle glaucoma Hyphema – Blood accumulation (blunt trauma) can occlude outflow trough the angle Factors Affecting IOP Injury to the TM Fuch’s endothelial dystrophy – Chronic dystrophy can lead to permanent damage to the TM Glaucomatocyclitic Crisis – Acute inflammation of the TM – Acute rise in IOP Angle recession glaucoma – Trauma to the iris with separation of the iris root – Microscopic damage to the TM - glaucoma Angle Structures Occlusive Factors Influencing in IOP Pseudoexfoliative Glaucoma – Aging epithelial cells of the iris and lens capsule can release pigment and pseudoexfoliative material – occlude the angle Pigment Dispersion Glaucoma – Pigment liberated from the posterior layer of the iris – damage to the trabecular fibrils – glaucoma Clinical Applications Uveitis – Breakdown in the blood aqueous barrier – Inflammation of the uveal tract – Iritis, cyclitis, iridocyclitis and choroiditis – Panuveitis (entire uvea) – Retina, cornea, vitreous and sclera can be involved – Unilateral or bilateral – Isolated attacks or repeated episodes – Autoimmune disease tends to be bilateral – Infectious disease or idiopathic often unilateral – Causes: AIDS, ankylosing spondylitis, Herpes, Sarcoidosis, Tuberculosis, Brucellosis, Inflammatory bowel disease, Rubella, Syphilis, Toxoplasmosis, Candidiasis, Cysticercosis, Polyarthritis Nodosa, Histoplasmosis, etc.

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