Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

186 CHAPTER 7 Cornea

Clinical features

•Initially asymptomatic; mild ocular irritation, photophobia, and mild decrease VA in adulthood.

•Discrete clear epithelial vesicles; initially central but spread peripherally (sparing the limbus).

Treatment

Treatment is not usually required; however, rarely, lamellar keratoplasty may be considered in patients with significant photophobia or visual impairment.

CORNEAL DYSTROPHIES: STROMAL (1) 187

Corneal dystrophies: stromal (1)

Lattice dystrophy types I, II, III

These are rare autosomal dominant dystrophies involving the progressive deposition of amyloid in the corneal stroma and sometimes elsewhere in the body.

Type I is the most common form and is isolated to the eye. Type II forms part of familial systemic amyloidosis (Meretoja’s syndrome). Type III is rare, isolated to the eye, and is seen in patients of Japanese origin.

Pathophysiology

Type I lattice dystrophy is caused by a mutation in the keratoepithilin gene BIGH3 (Ch5q). Type II results from a mutation in the gene for the plasma protein gelsolin (Ch9q).

In all types, amyloid is deposited in the stroma, but in types I and II it may also disrupt the basement membrane and epithelium. Amyloid stains with Congo red and demonstrates birefringence and dichroism at polarizing microscopy.

Clinical features

•dVA, recurrent erosions (pain, lacrimation, photophobia).

•Bilateral (often asymmetric) criss-cross refractile lines; later these may be obscured by a progressive central corneal haze (types I and II).

In type III the lines are thicker and more prominent. The peripheral cornea is usually spared.

Systemic features

In type II there is lattice dystrophy with familial amyloidosis (Meretoja’s syndrome): mask-like facies, skin laxity, cranial nerve palsies (commonly CN VII with additional risk of corneal exposure), peripheral neuropathy, renal failure, and cardiac failure.

Treatment

Treatment is as for recurrent erosion syndrome (RES) (p. 180).

Consider PK or excimer laser keratectomy if decrease A. Recurrence after either procedure is common. If type II disease is suspected, refer to physician for assessment of systemic involvement.

Granular dystrophy

This is a rare autosomal dominant dystrophy involving deposition of hyaline material in the corneal stroma. It presents in adulthood.

Pathophysiology

Granular dystrophy is caused by a mutation in the keratoepithilin gene BIGH3 (Ch5q). Hyaline material (probably phospholipids) deposited in the stroma stains red with Masson trichrome.

Clinical features

•dVA; occasionally recurrent erosions

•Bilateral (often asymmetric) white crumb-like opacities in otherwise clear stroma; initially central but progressively coalesce

188 CHAPTER 7 Cornea

Treatment

Treatment is as for recurrent erosion syndrome (RES) (p. 180).

If there is dVA, consider PK, or lamellar keratoplasty for relatively superficial disease. Recurrence is common.

Avellino dystrophy

This is a very rare autosomal dominant dystrophy with some features of both granular and lattice dystrophies. It is usually seen in those originating from Avellino, Italy.

Pathophysiology

Avellino dystrophy is caused by a mutation in the keratoepithilin gene BIGH3 (Ch5q). The stromal deposit stains both for hyaline (Masson trichrome) and amyloid (Congo red; birefringence and dichroism by polarizing light microscope).

Clinical features

•dVA; recurrent erosions (pain, lacrimation, photophobia).

•Bilateral (often asymmetric) granular-type opacities in anterior stroma, and lattice-type lines in deeper stroma; may have a central subepithelial haze later.

Treatment

Treatment is as for recurrent erosion syndrome (RES) (p. 180).

Consider PK for dVA. Recurrence is common.

CORNEAL DYSTROPHIES: STROMAL (2) 189

Corneal dystrophies: stromal (2)

Macular dystrophy

This is a rare autosomal recessive dystrophy involving deposition of a glycosaminoglycan in the stroma. Abnormal stromal collagen packing causes loss of corneal translucency, usually from early adulthood.

Pathophysiology

This is effectively an ocular-specific mucopolysaccharidosis, arising from mutations in the gene for carbohydrate sulfotransferase (CHST6; Ch 16q). Abnormal glycosaminoglycans similar to keratan sulfate accumulate. These stain with Alcian blue or colloidal iron. Macular dystrophy may be subclassified as type I (no keratan sulfate) and type II (low keratan sulfate).

Clinical features

•Gradual painless dVA; this is often an incidental finding.

•Bilateral (often asymmetric) focal ill-defined gray-white stromal opacities superimposed on diffuse clouding. It may involve the whole cornea being superficial centrally, but potentially involving full stromal thickness peripherally. The cornea may be thinned.

Treatment

If dVA, consider PK, or lamellar keratoplasty for relatively superficial disease. Recurrence is rare.

Schnyder’s crystalline dystrophy

This is a rare progressive dystrophy presenting in childhood with an autosomal dominant inheritance pattern. Stromal crystals contain cholesterol and neutral fat (stains red with oil red O). It may be associated with systemic hypercholesterolemia.

Clinical features

•dVA, glare.

•Central anterior stromal yellow-white (often scintillating) crystals with associated corneal haze and arcus.

Treatment

Consider excimer laser keratectomy or PK if there is dVA. Recurrence may occur. Check fasting lipids.

Congenital hereditary stromal dystrophy (CHSD)

This is a very rare autosomal dystrophy that presents at birth with bilateral corneal clouding without edema. It is nonprogressive. It appears to arise from abnormalities of stromal collagen but with normal anterior and posterior corneal layers. Corneal thickness is normal.

Treatment requires penetrating keratoplasty.

CORNEAL DYSTROPHIES: POSTERIOR 191

Corneal dystrophies: posterior

Fuchs’ endothelial dystrophy (FED)

This common corneal dystrophy may be autosomal dominant or sporadic. It is more commonly seen in females (F:M 4:1) and with increasing age. Presentation is usually gradual with dVA from middle age but may be acute after endothelial injury (e.g., intraocular surgery). There appears to be an increased incidence of primary open-angle glaucoma (POAG).

Pathogenesis

Primary endothelial dysfunction associated with Na+K+ATPase pump failure allows the accumulation of fluid. Mutation in the gene for the collagen VIII A2 chain has been seen in patients with FED and with posterior polymorphous corneal dystrophy (PPMD). Microscopically, there is irregular thickening of Descemet’s membrane, protuberances (guttata), and flattening, irregularity in size, and loss of endothelial cells.

Clinical features

•Gradual dVA (often worse in morning); this may arise after intraocular surgery.

•Stage 1: corneal guttata (appear centrally cf. the peripheral Hassall–Henle bodies, which are normal with age); may extend to give beaten-metal appearance; pigment on endothelium.

•Stage 2: stromal edema lDescemet’s folds and epithelial bullae.

•Stage 3: recurrent corneal erosions lsubepithelial vascular pannus and stromal haze.

Investigations

Specular microscopy can show dcell count, iaverage cell diameter, dhexagons, and ivariation in cell size.

Treatment

Relieve corneal edema and improve comfort.

•Topical hypertonic agents: 5% NaCl.

•Treat ocular hypertension.

•Warm air blown on the eyes (e.g., hair dryer) in the morning.

•Bandage contact lens for bullous change.

Visual rehabilitation

Persistent corneal opacity may require PK. In the presence of coexisting cataract, a triple procedure is performed (i.e., combined PK, lens extraction, and posterior chamber intraocular lens [PCIOL] insertion). In the absence of any stromal scarring, Descemet’s stripping endothelial keratoplasty (DSEK) is an option.

Prevention

Corneal decompensation may be inadvertently accelerated by the ophthalmologist:

•Cataract surgery: consider 1) protecting the endothelium with additional heavy viscoelastic (soft shell technique) and minimizing phaco-time, and 2) referral of more severe cases to a corneal

192 CHAPTER 7 Cornea

specialist for elective simultaneous PK, cataract extraction, and IOL (a triple procedure). Careful patient counseling regarding risk of decompensation is essential prior to surgery.

•Ocular hypertension/glaucoma: topical B-blocker is preferred; topical carbonic anhydrase inhibitors may induce endothelial failure.

Congenital hereditary endothelial dystrophy (CHED)

CHED is an important cause of bilateral corneal edema in otherwise healthy term neonates (p. 617). It is usually autosomal recessive. An autosomal dominant variant has been linked to the same region (Ch20q) as posterior polymorphous dystrophy (PPMD). It appears to be a dysgenesis in which neural crest cells fail to complete differentiation into normal endothelium.

Clinical features

Autosomal recessive type

Bilateral marked corneal edema occurs from birth. Stroma is up to 3x normal thickness. There is severe dVA, amblyopia, and nystagmus; it is not usually painful.

Autosomal dominant type

Bilateral mild corneal edema occurs from infancy with tearing and photophobia. This type has milder dVA and no nystagmus; it is gradually progressive.

Treatment

Treatment is with PK; visual outcome is often limited by amblyopia.

Posterior polymorphous dystrophy (PPMD)

PPMD is usually autosomal dominant but has a very variable expression. It shares features with iridocorneal endothelial (ICE) syndrome and the anterior segment dysgenesis, all of which may form part of a continuum of failed neural crest terminal differentiation.

Clinical features

Clusters or lines of vesicles, irregular broad bands or diffuse haze of the posterior cornea ± iridocorneal adhesion, corectopia, glaucoma (closed or open angle).

Treatment

Treatment is not usually necessary. Consider penetrating keratoplasty if there is significant dVA.

CORNEAL ECTASIAS 193

Corneal ectasias

Keratoconus

This is a common corneal ectasia characterized by progressive conical distortion of the cornea with irregular astigmatism, axial stromal thinning, apical protrusion, and increasing myopia. Prevalence estimates vary widely (0.05–5%) according to the population studied, the techniques used, and the definition adopted.

The etiology is unclear but may be a combination of repeated trauma (e.g., eye-rubbing) and abnormalities of corneal stroma (e.g., in connective tissue disorders). Previously, only 10% cases were thought to be familial. However, analysis by videokeratography suggests a high prevalence among asymptomatic family members that is consistent with autosomal dominant inheritance with variable penetrance.

Keratoconus usually presents in early adulthood; an earlier presentation is associated with a worse prognosis.

Risk factors

Table 7.11 Associations of keratoconus

Clinical features

•Usually bilateral (but asymmetric) progressive irregular astigmatism with dVA. Progression continues into early adulthood but usually stabilizes by mid-30s.

•Corneal steepening/thinning (cone), Vogt’s striae (vertical lines in the stroma that may disappear upon pressure), Fleischer ring (iron

deposition at base of cone), conical distortion of lower lid on downward gaze (Munson’s sign), abnormal focusing of a slit-lamp beam orientated obliquely across the cone from the temporal side (Rizutti’s sign), scissoring reflex on retinoscopy, oil droplet reflex on ophthalmoscopy.

•Complications: acute hydrops (Descemet’s membrane rupture with acute corneal edema, may result in scarring); corneal scar.

194 CHAPTER 7 Cornea

Investigations

•Videokeratography: This has largely replaced manual keratometry. It is used for diagnosis and monitoring of disease. It may also classify keratoconic changes according to:

Severity: mild (<48D), moderate (48–54D), and severe (>54D). Morphology: cone, nipple, oval, bowtie, and globus.

Treatment

Counsel patient on the progressive nature of the disease, frequent changes in refractive error, and the potential impact on lifestyle (notably driving) and career. Since disease usually stabilizes by the mid-30s, a patient with good VA at age 35 is unlikely to need a keratoplasty.

•Mild astigmatism: spectacle or contact lens correction.

•Moderate astigmatism: rigid gas permeable lens (8.7–14.5 mm), scleral lens (PMMA).

•Severe astigmatism: deep lamellar keratoplasty (if normal Descemet’s membrane) or penetrating keratoplasty. 90% of patients with keratoconus achieve clear grafts, but postoperative astigmatism ± anisometropia often necessitate additional contact lens use.

Keratoglobus

This is a very rare bilateral ectasia characterized by global corneal thinning and significant risk of rupture at minor trauma. It may be acquired (probably as an end-stage keratoconus) or congenital (autosomal recessive associated with Ehlers–Danlos type VI and brittle cornea syndrome).

Treatment includes protection from trauma, scleral contact lenses, and sometimes lamellar epikeratoplasty.

Pellucid marginal degeneration

This is a rare bilateral progressive corneal ectasia of the peripheral cornea. It results in crescenteric thinning inferiorly and marked against-the-rule astigmatism. It presents in the third to fifth decade with non-inflammatory, painless visual distortion. Hydrops is rare.

Treatment is with hard contact lenses; it is usually uncorrectable with eyeglasses. Surgical intervention is usually disappointing. Surgical techniques include eccentric penetrating keratoplasty, wedge resection, and lamellar keratoplasty.

Posterior keratoconus

This is a rare nonprogressive congenital abnormality of the cornea in which there is abnormal steepening of the posterior cornea in the presence of normal anterior corneal surface. It is usually an isolated unilateral finding, but may be associated with ocular (e.g., anterior lenticonus, anterior polar cataract) or systemic abnormalities.

Treatment is not usually necessary, but requires penetrating keratoplasty if there is significant dVA.

PERIPHERAL ULCERATIVE KERATITIS 195

Peripheral ulcerative keratitis

Peripheral ulcerative keratitis (PUK)

PUK is an aggressive sight-threatening form of keratitis that is sometimes associated with underlying systemic disease (Box 7.4). The etiology is uncertain, although the rheumatoid model suggests that immune complex deposition at the limbus causes an obliterative vasculitis with subsequent corneal inflammation and stromal melt (see Table 7.12).

Causes

Box 7.4 Causes of peripheral ulcerative keratitis

•Idiopathic.

•Rheumatoid arthritis (RA).

•Wegener’s granulomatosis.

•Systemic lupus erythematosus (SLE).

•Relapsing polychondritis.

•Polyarteritis nodosa.

•Microscopic polyangiitis.

•Churg–Strauss syndrome.

Clinical features

•Variable pain and redness (may be none); dVA.

•Unior bilateral peripheral ulceration with epithelial defect and stromal thinning; associated inflammation at the limbus (elevated, injected) associated scleritis.

•Systemic features (if associated disease) include degenerative joints (rheumatoid arthritis), saddle nose (Wegener’s granulomatosis), skin changes (psoriasis, scleroderma, systemic lupus erythematosus), and degenerative pinna cartilage (relapsing polychondritis).

Investigations

These are as directed by systemic review. Consider blood pressure (BP); complete blood count (CBC), erythrocyte sedimentation rate (ESR), urinalysis, liver function tests, Glu, C-reactive protein (CRP), vasculitis screen (including rheumatoid factor [RF], antinuclear antibody [ANA], antineutrophil cytoplasmic antibody [ANCA], dsDNA), cryoglobulins, hepatitis C serology; and chest X-ray.

Treatment

•Emergency referral to corneal specialist and involve patient’s physician and rheumatologist.

•Systemic immunosuppression (coordinate with rheumatologist) may include corticosteroids, methotrexate, mycophenolate, azathioprine, or cyclophosphamide.

•Topical immunosuppression: steroids (but use with caution in rheumatoid arthritis or if there is significant thinning since keratolysis may be accelerated) or cyclosporine.