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

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Lens

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1969

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Ciliary Body and Choroid

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Optic Nerve

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NORMAL ANATOMY (Figs 16.1–16.3)

I.The outermost or corneoscleral layer of the eye can be separated into corneal and scleral portions by two circumferential grooves, a shallow outer one, the outer scleral sulcus, and a deeper inner one, the inner scleral sulcus.

A.The posterior boundary of the inner scleral sulcus is a ridge, mainly composed of circumferentially oriented bundles of collagen fibrils, the scleral roll or Schwalbe’s posterior-border ring.

B.After continuing a short distance posteriorly, the ridge or roll tapers and finally blends with the more predominant, obliquely arranged collagenous lamellae of the sclera.

C.Deep within this inner sulcus and applied closely to the collagenous tissue of the corneosclera lies the large vessel called the canal of Schlemm.

1.This circumferentially arranged branching vessel is formed by a continuous layer of nonfenestrated endothelial cells with a rather patchy or di use basement membrane.

2.The structure of the canal of Schlemm closely resembles the structure of a lymphatic.

3.It is called an aqueous vessel because in vivo it contains aqueous fluid alone.

4.The outer wall of the canal also rests on a basement membrane that is separated from the dense collagenous lamellae of cornea and sclera by a few loose cells.

5.The inner wall rests on a thinner or patchy basement membrane that is associated with a zone of delicate connective tissue, the juxtacanalicular connective tissue.

a.The juxtacanalicular connective tissue is a special zone of the corneoscleral trabecular meshwork and consists of cells surrounded by a variety of

fibrous and mucinous extracellular materials.

The juxtacanalicular connective tissue is irregular in thickness from front to back in any single meridional section; it is more delicate in the younger eye and more prominent in the adult eye.

b.Examination of trabeculectomy specimens containing the external portion of the trabecular meshwork reveals severely decreased cellularity in glaucoma.

6.Pores are present in the wall of Schlemm’s canal.

Their role, if any, in regulating aqueous outflow has not been established.

7.It is probable that a history of previous glaucoma filtration surgery and long-term high intraocular pressure (IOP) are associated with shortening of

Schlemm’s canal.

8.Ultrastructural analysis of ocular basement membrane components fails to demonstrate significant di erences between the characteristics of these structures in normal and glaucomatous eyes.

D.Large endothelium-lined channels (collector channels) connect the canal of Schlemm either anteriorly or, more commonly, posterior to the intrascleral venous plexus that drains both the canal of Schlemm and the longitudinal ciliary muscle.

If the collector channels reach the surface of the sclera unconnected, they can be observed in vivo as the clear aqueous veins (Ascher).

Fig. 16.1 Normal adult angle. Schematic representation of meridional section of corneoscleral coat. Circumferential shallow outer sulcus (1) and deeper, inner sulcus (2) are present in region of union of sclera with cornea. Posterior boundary of inner sulcus is thickened by scleral roll (posterior border ring of Schwalbe).

II.The trabecular meshwork

A.In meridional sections of a young eye, a loose collagenous meshwork can be seen filling the inner scleral sulcus and extending as an open fan to the root of the iris. The “handle” of this fan is located just anterior to the end of Descemet’s membrane—Schwalbe’s ante- rior-border ring—where a few layers of meshwork enter into and blend with the deep peripheral corneal stroma.

B.The meshwork may be easily and usefully separated into two parts by an imaginary line extending from the scleral roll to the end of Descemet’s membrane (see Fig.

16.2).

1.The meshwork lying external to the line and extending from cornea to sclera is known as the corneoscleral meshwork.

2.The meshwork lying internal to the line and in continuity with the uveal tract posteriorly is known as the uveal meshwork.

C.A single trabecula of uveal meshwork consists of a collagenous core surrounded by a single layer of polarized cells (“endothelium”—in reality a mesothelium).

1.A basement membrane separates the polarized endothelial cells from the underlying collagenous core and, not infrequently, patches of this basement

membrane present a periodic structure (banded basement membrane) measuring 100 nm (1000 → A).

D.Lying within the tightly packed collagenous cores of the trabeculae are many aggregates of filamentous and homogenous elastic tissue whose density increases with age.

Fig. 16.2 Normal adult angle. The trabecular meshwork is a loose collagenous meshwork that fills the inner scleral sulcus and extends as an open fan to the root of the iris. The meshwork may be separated into two parts by an imaginary line extending from the end of Descemet’s membrane (1) to the scleral roll (2). The meshwork lying external to the line and extending from cornea to sclera is known as the corneoscleral (cs) meshwork. The meshwork lying internal to the line and in continuity with the uveal tract posteriorly (3) is known as the uveal (u) meshwork. A third part, which rests on the inner wall of the canal of Schlemm (s), is a thin or patchy basement membrane associated with a zone of delicate connective tissue called the juxtacanalicular connective tissue (jct).

1.The aggregates also take the stains for elastic tissue.

2.As in other connective tissues, additional ground substance materials are probably present, but their identification and quantitation remain obscure.

E.The endothelial cells covering the connective tissue core have apical surfaces, line intertrabecular spaces, and therefore are bathed by aqueous.

F.The trabeculae of the meshwork are roughly arranged into circumferential sheets lying superimposed one on the other.

They can be fairly easily separated from one another mechanically, especially in the uveal meshwork. The spaces between adjacent sheets are called intertrabecular spaces. Large oval apertures traverse each trabecular sheet and may be called transtrabecular spaces. The transtrabecular apertures are not superimposed, and decrease in size in the direction of the corneoscleral meshwork. The corneoscleral sheets differ only slightly from the uveal in having somewhat flatter trabeculae as observed in cross-section and in lacking the staining characteristics for elastic fibers. The transtrabecular apertures here are more circular and smaller than those of the uveal meshwork. All intertrabecular and transtrabecular spaces thus may be considered extensions of the anterior chamber.

G.Spaces between individual sheets are well seen in proper meridional section, and here are termed the intertrabecular spaces.

In the uveal meshwork, the intertrabecular spaces pass the scleral roll to continue with the tissue spaces lying between the smooth-muscle cells of the ciliary muscles—especially those of the meridional (longitudinal) ciliary muscle. If serially sectioned in a frontal or coronal plane, the spaces can be seen as large-apertured, relatively straight, short tubes. Such a grouping of tubes with apertured walls might be termed a system of compound aqueous tubes. In the corneoscleral meshwork, which blends posteriorly with the region of the scleral roll, the intertrabecular spaces (tubes) abut the canalicular extensions of the canal of Schlemm. Such extensions are frequent in this region.

H.The blind inpouchings of the canal of Schlemm (canals of Sondermann), here termed canaliculi, are endothe- lium-lined, and do not appear to be in continuity with the intertrabecular spaces. Their function, presumably, is to drain o aqueous passing laterally along the corneoscleral trabecular meshwork (i.e., along the intertrabecular spaces).

I.The presence of adenylate cyclase subtypes II and IV in the human aqueous outflow pathway suggests that cholinergics may exert an e ect on outflow facility, mediated by cyclic adenosine monophosphate (cAMP), that is independent of muscle contraction.

III.The roles of various genes in the development of the forms of glaucoma are beginning to be elucidated. Specific genes that may play such a role are Bmp4, Cyp1b1, Foxc1, Foxc2, Pitx2, Lmx1b, and Tyr. Similarly, specific gene products, such as growth factors, may be implicated in the development of glaucoma.

INTRODUCTION

Six genetic loci have been recognized to date (GLC1A–GLC1F) as contributing to glaucoma. A glaucoma-causing gene has been identified at two of these loci—GLC1A and GLC1E, and

sequence variations in the optineurin (OPTN) gene on GLC1E have been found to be associated with the development of normal-tension glaucoma in at least nine separate families.

The E50K mutation in the optineurin gene is associated with increased severity of normal-tension glaucoma. There may be racial di erences in glaucoma-associated optineurin genotypes.

In families with the GLC1A Gln368STOP mutation, agerelated penetrance for ocular hypertension or primary open-angle glaucoma (POAG) was 72% at age 40 years, and 82% at age 65 years. In general, individuals with the mutation have an earlier age at onset, higher peak IOP, and are more likely to have undergone filtration surgery than nonmutation glaucoma patients.

I.Glaucoma is characterized by an IOP su cient to produce ocular tissue damage, either transient or permanent.

A.Glaucoma is a “family” of diseases having in common a type of optic atrophy called optic nerve head cupping or excavation.

1.Various systemic abnormalities have been associated with glaucoma, including elevation of the 20S proteasome alpha-subunit of leukocytes.

2.The appearance of the optic disc is an important diagnostic finding in glaucoma. The ratio of the optic cup :disc is moderately heritable.

A more appropriate name may be glaucomatous optic neuropathy because the primary defect, especially in chronic open-angle glaucoma, appears to be within the optic nerve head. High IOP (>25 mmHg), or the presence of glaucoma, is a marker for decreased life expectancy.

B.Although most individuals associate glaucoma with an elevated IOP, the pressure may, in fact, be within the statistically “normal” range and still cause ocular tissue damage in normal-tension (improperly called lowtension) glaucoma.

1.IOP is a risk factor for glaucoma, and the higher the pressure, the greater the probability of the development of the disorder.

a.The accurate measurement of IOP is vital to the proper diagnosis and treatment of glaucoma.

b.Central corneal thickness (CCT) impacts the validity of IOP measurements, particularly in the diagnosis of ocular hypertension. Thicker corneas, comprised of normal corneal tissue, produce an artificially high IOP measurement compared to manometrically measured “true” IOP. Conversely, corneas that are thinner than normal produce an inappropriately low pressure measurement.The impact of CCT on IOP measurement varies with the type of tonometer employed for the measurement. Refractive surgery can alter the validity of tonometry through several mechanisms, including change in corneal thickness and creating a fluid interface between the flap and the residual stroma.

Corneal thickness also probably correlates with

glaucoma progression and visual field loss, although this relationship has been questioned.

Decreased CCT is present in normal-tension glaucoma and thinner than in POAG. Similarly, CCT is thinner in patients with vascular risk factors for glaucoma. Patients with congenital aniridia have CCT that is significantly thicker than normal. This abnormality is not secondary to corneal edema resulting from endothelial dysfunction.

c.CCT is increased in children with ocular hypertension.

d.There is considerable racial variation in CCT.

e.Osteogenesis imperfecta may be associated with an abnormally thin CCT.

f.Alterations in corneal thickness related to forkhead gene dosage can result in errors in IOP measurement. Increased CCT is associated with segmental gene duplication.

g.In the past, individuals having thinner than normal corneas that have led to spuriously low

IOP measurements have probably been included in the population said to have normal-pressure glaucoma. Conversely, some individuals with thicker than normal corneas that produced artificially elevated IOP measurements, but who had true IOP within the normal range, were probably included in the population classified as ocular hypertensives (see below).

Glaucoma, therefore, is not an IOP reading, it is a syndrome. In fact, the cause of the glaucoma may be due to factors (mostly poorly understood) other than IOP (i.e., IOP is simply one risk factor).

2.Normal-tension glaucoma probably accounts for approximately one-third of all cases of POAG.

Disc hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma.

3.OPA1 on chromosome 3 is the gene responsible for dominant optic atrophy. It encodes for a mitochondrial metabolic protein. Some cases of normaltensionglaucomaareassociatedwithpolymorphisms of the OPA1 gene. This association raises the possibility that normal-tension glaucoma may result from mitochondrial dysfunction.

4.Over 6% of patients with normal-tension glaucoma may have relevant intracranial compressive lesions.

Such lesions are usually lacking in POAG.

5.Predictive factors for progression of normal-tension glaucoma di er from those of POAG, possibly suggesting di erent pathobiologic mechanisms for these disorders.

6.Plasma levels of the 20S proteasome alpha-subunit are significantly increased in glaucoma patients

compared to control patients, and is even more elevated in normal-tension glaucoma patients.

Papillorenal syndrome is associated with optic disc and visual field anomalies that may lead to an erroneous diagnosis of normal-tension glaucoma.

II.Glaucoma suspect

A.Increased IOP without detectable ocular tissue damage or visual functional impairment is called ocular hypertension. An individual who has some features of glaucoma, but in whom a definitive diagnosis has not yet been confirmed, is termed a glaucoma suspect.

B.Ocular hypertension may be tolerated by the person or, eventually, may lead to ocular tissue damage and hence to glaucoma.

The prevalence of glaucoma suspect is approximately 8%. The incidence of glaucoma among glaucoma suspects is approximately 1% per year.

III.Glaucoma is the leading cause of blindness among the 500 000 legally blind people in the United States—approx- imately 14% (1 in 7) of blind people.

The second leading cause of blindness is retinal disease (exclusive of diabetic retinopathy), mainly age-related macular degeneration, followed by cataract. Optic nerve disease is fourth; diabetic retinopathy, fifth; uveitis, sixth; and corneal and scleral disease, seventh. Leading causes of new cases of blindness, in order of importance, are macular degeneration, glaucoma, diabetic retinopathy, and cataract.

A.Glaucoma of all types a ects approximately 0.5% to 1% of the general population, 2% of people age 35 years or older, and 3% of people age 65 years or older.

B.POAG accounts for approximately two-thirds of all glaucoma seen in white patients.

1.The prevalence of POAG in white patients ranges from approximately 0.9% in people 40 to 49 years of age to approximately 2.2% in those 80 years of age or older.

2.The prevalence of POAG in black patients ranges from approximately 1.2% in people 40 to 49 years of age to approximately 11.3% in those 80 years of age old or older.

3.The prevalence of POAG and ocular hypertension in adult Latinos ≥40 years is about 4.7% and 3.6%, respectively.

IV. Primary closed-angle glaucoma, which has a prevalence of less than 0.5%, is much less common in black patients than in white patients. A high percentage of black patients who develop angle closure, however, have chronic closed-angle glaucoma instead of the acute type.

The prevalence of primary closed-angle glaucoma is highest amongst Inuits (approximately 2% to 3%), followed by Asians (approximately 1%).

V.There is considerable racial variation in the incidence and prevalence of the various forms of glaucoma.

NORMAL OUTFLOW

Hypersecretion

I.Hypersecretion glaucoma is rare and has no antecedent cause.

II.Outflow facility is normal. The elevated IOP is presumed to be caused by an increased production of aqueous

humor.

III.The glaucoma mainly a ects middle-aged women, especially when they have neurogenic systemic hypertension.

IV. Histologically, the angle of the anterior chamber shows no abnormalities.

IMPAIRED OUTFLOW

Congenital Glaucoma

I.General information

A.The rate of congenital glaucoma is from 1 :5000 to

1 :10 000 live births.

B.It is usually inherited as an autosomal-recessive trait, but can have an infectious cause (e.g., rubella).

C.Approximately 60% to 70% of a ected children are boys.

D.The disease is bilateral in 64% to 88% of cases.

E.Age of onset

1.Present at birth: 40%

2.Between birth and 6 months: 34%

3.Between 6 months and 1 year: 12%

4.Between 1 year and 6 years: 11%

5.Over 6 years: 2%

6.No information: 1%

Primary juvenile glaucoma can be arbitrarily defined as an autosomal-dominant syndrome, not associated with any other ocular or systemic abnormalities, and occurring between the ages of 3 and 20 years. One gene responsible for this condition, called the GLCIA gene, has been localized to the 1q21–q31 region of chromosome 1. The same mutation has been found in 2.9% of patients with openangle glaucoma (see below).

II.Pathogenesis (many theories)

A.Barkan’s membrane (mesodermal surface membrane or imperforate innermost uveal sheet) mechanically prevents the aqueous from leaving the anterior chamber

(histologic proof for this theory is scarce).

B.Congenital absence of Schlemm’s canal

1.Congenital absence of Schlemm’s canal is very rare, if it exists at all.

2.Most often, the canal is compressed or collapsed as a secondary change resulting from chronically elevated IOP. The canal, therefore, may be di cult to find histologically.

C.An “embryonic” anterior-chamber angle that results from faulty cleavage of tissue during embryonic development of the eye prevents the aqueous from leaving the anterior chamber.

1.Histologically, the angle shows an anterior “insertion” of the iris root, anteriorly displaced ciliary processes,insertion of the ciliary meridional muscles into the trabecular meshwork instead of into (or over) the scleral roll, and mesenchymal tissue in the anterior-chamber angle (Fig. 16.4).

2.Many nonglaucomatous infant eyes show a similar anterior-chamber angle structure.

3.To interpret angle histology accurately, it is necessary to study truly meridional sections through the anterior-chamber angle.

a.Tangential sectioning makes interpretation difficult (see Fig. 16.4C and D).

b. Unfortunately, in the usual serial sectioning of a whole eye, because of the continuously curved surface, only a few sections from the center of the embedded tissue are truly meridional.

D.The true cause or causes of congenital glaucoma probably remain unknown.