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

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NORMAL ANATOMY

I.The conjunctiva (Fig. 7.1) is a mucous membrane, similar to mucous membranes elsewhere in the body, whose surface is composed of nonkeratinizing squamous epithelium, intermixed with goblet (mucus) cells, Langerhans’ cells (dendritic-appearing cells expressing class II antigen), and occasional dendritic melanocytes. Stem cells for the epithelium are located near the limbus and their loss can result in exhaustion of the conjunctival epithelial population. Such stem cell loss may have many causes, including the use of mitomycin C in glaucoma filtration surgery, which may be exhibited as a late complication.

A.Idiopathic stem cell deficiency is rare, most commonly found in women, and may be familial in some cases. Patients exhibit severe photophobia and, on clinical examination, have corneal vascularization accompanied by loss of the limbal palisades of Vogt, hazy peripheral corneal epithelium, and the presence of conjunctival goblet cells by impression cytology.

A conjunctivalized pannus may develop on the cornea of those with total limbal stem cell deficiency. Characterization of this tissue demonstrates that it is not corneal, as evidenced by failure to stain for corneaspecific K12 mRNA and protein, but rather, it is conjunctival, as evidenced by the presence of goblet cells, the weak expression of K3, and the strong expression of K19.

B.The homeostasis of the conjunctiva is dependent, in part, on the maintenance of a normal tear film, which is comprised of lipid, aqueous, and mucoid layers. Multiple disorders are associated with abnormal tear quantity and/or quality, and secondary ocular surface changes.

1.Cigarette smoking has a deteriorating e ect on the tear film in general, and on its lipid layer in particular. It results in decreased quantity and quality of the tear film, decreased corneal sensitivity and squamous metaplasia, and this deterioration is related to the amount of smoking.

2.Tear film abnormalities have been documented in association with pseudoexfoliation syndrome and pseudoexfoliation glaucoma, and are reflected in abnormal conjunctival impression cytology and altered goblet cell morphology.

3.Although ocular surface glycocalyx is normally present in conjunctival epithelium, it is generally absent in patients with Sjögren’s syndrome who have accompanying ultrastructural abnormalities of the apical conjunctival epithelium. Conjunctival biopsy specimens from patients with Sjögren’s syndrome and non-Sjögren’s keratoconjunctivitis sicca demonstrate lymphocytic infiltration and increased immunoreactivity for markers of immune activation.

4.The pattern of human leukocyte antigen (HLA)- DR expression in mild and moderate dry eyes appears to reflect disease progression, and suggests that inflammation may be a primary cause of ocular surface damage.

5.Abnormal tear film stability and meibomian gland dysfunction are associated with aniridia, and correlate with the severity of the disease. Impression cytology has confirmed varying degrees of limbal stem cell deficiency in these patients.

6.Squamous metaplasia of the ocular surface epithelium and ocular tear function abnormalities have been associated with interferon and ribavirin treatment for hepatitis C.

7.Conjunctiva in beta-thalassemia exhibits goblet cell loss and conjunctival squamous metaplasia.

8.There is increased expression of conjunctival epithelial beta-defensin-2 in patients with moderately dry eye, suggesting that the disorder may be mediated by proinflammatory cytokine activity.

9.Complete androgen-insensitivity syndrome may promote meibomian gland dysfunction and increase the signs and symptoms of dry eye.

10.The ocular surface disease in keratoconus is characterized by abnormal tear quality, squamous metaplasia, and goblet cell loss, all of which appear to relate to the extent of keratoconus progression.

11.In patients with dry eyes, the degree of conjunctival metaplasia, characterized by increased stratification, epithelial cellular size, and a general loss of goblet cells, correlates with the clinical severity of their disorder.

12.Marx’s line represents a narrow line of epithelial cells posterior to the tarsal gland orifices along the lid marginal zone, averaging 0.10 mm in width, and is stained with lissamine green dye. It is believed to be the natural site of frictional contact between the eyelid margin and the surfaces of the bulbar conjunctiva and cornea, rather than the edge of the tear meniscus or location of the edge of the lacrimal river.

II.The conjunctival epithelium rests on a connective tissue, the substantia propria.

III.The conjunctiva is divided into three zones: tarsal, fornical–orbital, and bulbar.

A.The substantia propria of the tarsal conjunctiva adheres tightly to the underlying tarsal connective tissue, whereas the substantia propria of the bulbar conjunctiva (and even more so the fornical–orbital conjunctival substantia propria) adheres loosely to the underlying tissue

(the fornical–orbital conjunctiva being thrown into folds).

The bulbar conjunctiva inserts anterior to Tenon’s capsule toward the limbus. Small ectopic lacrimal glands of Krause are found in both the upper and lower fornices, with very few on the nasal side; glands of Wolfring are found around the upper border of the tarsus in the nasal half of the upper lid, and in lesser numbers, in the lower lid near the lower tarsal border; and glands of Popoff reside in the plica semilunaris and caruncle.

B.The periodic acid–Schi (PAS) stain-positive goblet cells are most numerous in the fornices, the semilunar fold, and the caruncle. The latter is composed of modi-

fied conjunctiva containing hairs, sebaceous glands, acini of lacrimal glandlike cells, globules of fat, on occasion smooth-muscle fibers, and rarely cartilage.

C.The tarsal conjunctiva meets the keratinized squamous epithelium of the skin on the intermarginal surface of the lid near its posterior border.

CONGENITAL ANOMALIES

Cryptophthalmos (Ablepharon)

See p. 169 in Chapter 6.

Epitarsus

I.Epitarsus consists of a fold of conjunctiva attached to the palpebral surface of the lid or lids of one or both eyes. The

fold has a free edge, and both surfaces (front and back) are covered by conjunctival epithelium.

II.Histologically, the folded conjunctival tissue looks like normal conjunctiva except for the occasional presence of islands of cartilage.

Hereditary Hemorrhagic Telangiectasia

(Rendu–Osler–Weber Disease)

I.It is a generalized vascular dysplasia characterized by multiple telangiectases in the skin, mucous membranes, and viscera, with recurrent bleeding and an autosomaldominant inheritance pattern.

No evidence of abnormalities in platelet aggregation or of qualitative abnormalities of factor VIII complex is found. Conjunctival hemorrhagic telangiectasia can give rise to “bloody tears.” Occasionally, telangiectases are observed in the retina and may mimic hypertensive or diabetic retinopathy.

II.Dilated conjunctival blood vessels, frequently in a star or sunflower shape, may appear at birth but are not usually fully developed until late adolescence or early adult life.

III.Histologically, abnormal, dilated blood vessels are seen in the conjunctival substantia propria.

Ataxia–Telangiectasia (Louis–Bar Syndrome)

See p. 36 in Chapter 2.

Congenital Conjunctival Lymphedema (Milroy’s

Disease, Nonne–Milroy–Meige Disease)

I.This condition of hypoplastic lymphatics is characterized by massive edema, mainly of the lower extremities and rarely of the conjunctiva, and has an X-linked recessive inheritance pattern.

A.Mutations in the kinase domain of the vascular endothelial growth facor receptor-3 (VEGFR3) gene cause Milroy disease

B.Late-onset hereditary lymphedema may be associated with distichiasis (lymphedema–distichiasis syndrome) and has an autosomal-dominant inheritance pattern.

Lymphedema–distichiasis syndrome has been mapped to 16q23 and to mutations in the FOXC2 gene.

II.The disease is thought to be due to a congenital dysplasia of the lymphatics, resulting in chronic lymphedema.

III.Histologically, dilated lymphatic channels and edematous tissue are seen.

Dermoids, Epidermoids, and Dermolipomas

See p. 240 in this chapter and p. 540 in Chapter 14.

Laryngo-Onycho-Cutaneous (LOC or Shabbir) Syndrome

I.LOC is an autosomal-recessive epithelial disorder characterized by cutaneous erosions, nail dystrophy, and

exuberant vascular granulation in certain epithelia, especially the conjunctiva and larynx.

II.It is confined to the Punjabi Muslim population, and is caused by an unusual N-terminal deletion of the laminin alpha3a isoform, thereby demonstrating that the laminin alpha3a N-terminal domain is a key regulator of the granulation tissue response. The protein product is secreted by basal keratinocytes of stratified epithelia, and it has been postulated that LOC results from a dysfunction of kerati- nocyte–mesenchymal communication.

VASCULAR DISORDERS

Sickle-Cell Anemia

See p. 412 in Chapter 11.

I.In homozygous sickle-cell disease, conjunctival capillaries may show widespread sludging of blood, and the venules may show saccular dilatations.

II.The characteristic findings (marked in SS disease and mild in SC disease), however, are multiple, short, comma-shaped