Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

A similar process, called melanocytomalytic glaucoma, has been reported with necrotic iris melanocytomas.

b.The liberated melanin induces phagocytosis by macrophages.

c.The melanin-laden macrophages then obstruct the open angle of the anterior chamber.

4.Epithelialization or endothelialization of anterior-

chamber angle (see pp. 119–120 in Chapter 5)

5. Di use iris melanoma presents with glaucoma in 56% of cases, and 32% of cases have had laser or incisional glaucoma surgery at the time of presentation.

II.Secondary to damaged outflow channels

A.Old uveitis may result in “scarring” of the tissues in the drainage angle.

B.Repeated attacks of acute closed-angle glaucoma may cause damage to the trabecular meshwork so that, even though the angle appears open, the facility of outflow is decreased.

C.Repeated hyphema may damage the aqueous outflow tissue.

D.In both siderosis and hemosiderosis bulbi, iron has a “toxic,” sclerosing e ect on tissues within the drainage angle.

E.Trauma

1.It may have a direct e ect on the tissues of the drainage angle by inducing scarring (sclerosis) of the trabecular meshwork, or it may cause a postcontusion deformity of the anterior-chamber angle (see pp. 136–138 in Chapter 5).

2.Iris melanocytes may proliferate over the trabecular meshwork and occlude an open anterior-chamber angle.

F.Cornea guttata (see p. 305 in Chapter 8)

G.In early iris neovascularization, before peripheral anterior synechiae form, an open anterior-chamber angle may be obstructed by an almost transparent, delicate

fibrovascular membrane arising from vessels near the iris root or near the anterior face of the ciliary body.

III.Secondary to corneoscleral and extraocular diseases such as interstitial keratitis, orbital venous thrombosis, cavernous sinus thrombosis, carotid–cavernous fistula, encircling band after retinal detachment surgery, retrobulbar mass, leukemia, and mediastinal syndromes

Carotid–cavernous fistula may also cause closed-angle glaucoma by a pupillary-block mechanism.

IV. Unknown mechanisms (usually reversible)

A.Corticosteroid-induced glaucoma (either oral or inhaled)

1.Aqueous humor endothelin-1 concentration is increased in human and animal models of POAG.

This increased concentration could result in increased release of nitric oxide, thereby resulting in increased contraction and decreased relaxation of the trabecular meshwork, and contribute to a decline in conventional aqueous outflow and the increased IOP seen in patients taking topical steroids.

2.Glucocorticoids can induce myocilin production in human and monkey trabecular meshwork cells and tissues.

3.Dexamethasone treatment does not enhance myocilin expression in corneal fibroblasts as it does in trabecular meshwork cells, and it is not associated with mitochondria in corneal fibroblasts. These differences may explain the di erential impact of steroids on the trabecular meshwork compared to other ocular tissues, even though myocilin is expressed in those tissues.

B.α-Chymotrypsin-induced glaucoma

C

TISSUE CHANGES CAUSED BY ELEVATED INTRAOCULAR PRESSURE

Cornea (Figs 16.26 to 16.28; see also Fig. 8.50)

I. Edema of stroma and epithelium (see Fig. 16.26)

II. Epithelial bullae (bullous keratopathy; see Fig. 16.26)

III.Corneal ulcer

A.The blebs of bullous keratopathy may rupture, causing the cornea to be susceptible to infection and corneal ulcer.

B.The corneal ulcer can result in corneal perforation, and even in an expulsive hemorrhage (see Figs 10.5, 16.27, and 16.28).

C.Corneal ulcer and associated sequelae are common

findings in blind, painful, glaucomatous eyes that come to enucleation.

IV. Degenerative subepithelial pannus

A.Histologically, the corneal edema is best seen in its earliest stage as a swelling and pallor of the basal layer of the epithelium.

B.Increased edema causes the basal layer of cells to swell more (clinically observed as corneal bedewing), causing a form of microcystoid degeneration.

C.The edema then spreads to overlying (anterior) epithelial cells.

D.Further accentuation of the edema ruptures the cell membranes, and macrocysts result.

E.At the same time, the epithelium is lifted o the underlying Bowman’s membrane by collections of fluid.

1.The overlying epithelium then appears irregular with areas of atrophy and hypertrophy.

2.The basement membrane of the epithelium is usually irregular.

F.With chronic edema, fibrous or fibrovascular tissue grows between epithelium and Bowman’s membrane, and forms a pannus.

G.Ultimately, the vascular component regresses completely, any inflammatory cells disappear, and a relatively acellular scar, a degenerative pannus, remains between epithelium and Bowman’s membrane.

V.Atrophy of epithelium and endothelium

VI. Hypertrophy of corneal nerves

VII. Corneal vascularization (Fig. 16.29)

Anterior-chamber angle

I.“Scarring” (sclerosis) of the tissues of the drainage angle results from chronic glaucoma.

II.Proliferation of corneal endothelium over the anteriorchamber angle (e.g., in postcontusion deformity of the anterior-chamber angle) or over the pseudoangle formed by a peripheral anterior synechia is commonly seen in enucleated glaucomatous eyes.

Iris

I.Dispersion of pigment onto and from the iris

Melanin pigment liberated from pigment epithelium or uveal melanocytes does not usually exist “free” on surfaces but is present in cells (e.g., in macrophages in iris, or in endothelium on posterior cornea or trabecular meshwork).

II. Fibrosis of stroma

III.Atrophy or necrosis of stroma dilator muscle and pigment epithelium

IV. Ectropion uveae (usually secondary to neovascularization of iris*)

V.Iris hyperpigmentation is a side-e ect of topical prostaglandin therapy for glaucoma. Histologic evaluation of involved irides demonstrates increased melanin production by melanocytes without melanocytic proliferation or atypia.

*Neovascularization of the iris is rare, if it occurs at all, in cases of primary open-angle glaucoma that have not had intraocular surgery or retinal vascular occlusion. It may occur in cases of primary closed-angle glaucoma, even without intraocular surgery, but with central retinal vein thrombosis.

Ciliary Body

I. Fibrosis and hyalinization of the core of fibrovascular tissue in the ciliary processes of the pars plicata

II. Atrophy of pars plicata

Lens

Cataract, especially after glaucoma surgery or after an acute attack of glaucoma (e.g., glaukomflecken with acute closed-angle glaucoma)

Sclera

Ectasia (thinning) or, if lined by uvea, staphyloma (Fig. 16.30)

Neural Retina (Fig. 16.31)

I.Degeneration of inner layers, predominantly nerve fiber and ganglion cell layer.

A.Mechanisms that have been proposed for the apoptotic cell death of RGC in glaucoma include neurotrophic factor deprivation, glutamate excitotoxicity, ischemia, glial cell activation, and immune response.

B.The presence of the proline form of p53 codon 72 appears to be a significant risk factor for the development of POAG. The p53 gene helps regulate apoptosis, which contributes to the pathobiology of glaucomatous optic neuropathy.

C.Blocking RGC apoptosis utilizing recombinant adenoassociated viral vector coding for human baculoviral IAP repeat-containing protein-4 (BIRC4), which is a potent caspase inhibitor, promotes optic nerve axon survival in a rat model for glaucoma.

II.Retinal ganglion cell loss (particularly a ecting small ganglion cells and those directly adjacent to the optic nerve) may be present in glaucoma. The implications for these

findings on the pathobiology of glaucoma are not known; however, these ganglion cells may influence blood flow regulation in the lamina cribrosa region of the optic nerve.

A link exists between apoptosis of RGC, matrix metalloproteinase (MMP-9), laminin degradation, and IOP. Abnormal ECM remodeling in the glaucomatous retina may relate to RGC death. Corpora amylacea in the RGC layer may decrease in number with advancing glaucoma. Autopsy eyes from one patient with normal-tension glaucoma showed immunoglobulins G and A deposition in the RGC, and inner and outer retinal layers, and apoptotic retinal cell death. The significance of these findings is not clear.

III.Photoreceptors are not lost in substantial numbers in POAG.

IV. There is gliosis, especially with secondary glaucoma.

V.Changes in macular thickness and volume correlate with the severity of glaucoma.

Optic Nerve

I.The normal optic nerve fiber count decreases with advancing age, with a mean annual loss of approximately 400 000

fibers; this process is accelerated by glaucoma.

II.Optic nerve atrophy results from a loss of the nerve fibers of the inner neural retina and optic nerve.

A.Whether the neural damage is caused by local or distant astrocytic damage or by vascular insu ciency is not known.

1.Astrocyte metabolism related to neurosteroids,

MMP-9, myocilin/TIGR and other cellular products are altered in glaucoma or in cells cultured at elevated IOP.

B.Also unknown is the exact e ect or role the blockage of axoplasmic transport (flow) has on the process.

C.Although optic nerve cupping and atrophy result from glaucoma, some cupping may not result from permanent axonal damage. For example, cupping may be reversible in congenital glaucoma following normalization of IOP, particularly in younger patients. Improved neural rim area can also be seen after IOP normalization, even in adults.

D.Polymorphisms in the OPA1 gene may be associated with the optic neuropathy of normal-tension glaucoma. Nevertheless, phenotypic di erences are not noted in

normal-tension glaucoma patients with and without

OPA1 (IVS 8 +4 C/T; +32T/C) genotype. The OPA1 locus is also associated with autosomal-dominant optic atrophy, which can be confused with normal-tension glaucoma.

E.Increased mRNA and protein levels for the ironregulating proteins transferrin, ceruloplasmin, and fer-

ritin are present in glaucoma, suggesting a role for the involvement of iron, copper, and associated antioxidant systems in its pathogenesis.

III.Atrophy results in loss of substance from the optic nerve head, leading to cupping (Fig. 16.32) or, if the loss is extensive, to excavation of the optic nerve head. Cup

enlargement, in turn, results in increased visibility of lamina cribrosa pores.

IV. Cavernous (Schnabel’s) optic atrophy (Fig. 16.33) consists of cystoid spaces, usually posterior to scleral lamina cribrosa. The cystoid spaces are filled with hyaluronic acid

(see p. 514 in Chapter 13).

Vitreous passes through the atrophic optic nerve head into the substance of the scleral portion of the optic nerve. Changes resembling Schnabel’s optic atrophy have been seen in nonglaucomatous eyes that contain primary or metastatic melanomas.

V.Parapapillary chorioretinal atrophy is associated with glaucoma.

A.Alpha parapapillary chorioretinal atrophy shows irregular hypopigmentation and hyperpigmentation.

B.Beta parapapillary chorioretinal atrophy shows complete chorioretinal atrophy with visible large choroidal vessels and sclera.

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