Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
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4)Endothelium
j)Congenital hereditary endothelial dystrophy.
k)Fuchs dystrophy.
l)Posterior polymorphous dystrophy.
Corneal epithelium is rich in genetic protein product keratoepithelin. Variations in the aggregation or precipitation of the several mutant forms of keratoepithelins in the cornea result in granular, lattice, avellino and Reis Buckler dystrophy.
Meesman's Dystrophy
It is characterized by presence of myriad small punctate vacuoles in the corneal epithelium. HPE- both corneal epithelium and its basement membrane are thickened. Epithelium has a disorderly appearance and contains cells that have a hyalinized appearance with small intra epithelial cystoid spaces.
Anterior Basement Membrane Dystrophy and Map-dot Finger
Print Dystrophy
It shows spectrum of epithelial abnormalities likereduplication, intraepithelial segments of corneal epithelial basement membrane, intraepithelial cystoid spaces filled with devitalized cellular debris and focal epithelial scarring. The subtypes are-
Cogan's microcystic dystrophy- shows multiple intraepithelial cysts filled with white putty like cellular debris. The devitalized cells that fill the cystoid spaces are trapped by duplication of the epithelium, which prevents their desquamation.
Finger print subtype shows parallel lines representing basement membrane material separating sheets of duplicated epithelium.
Map like changes are due to irregular, geographically shaped areas of subepithelial scarring. Corneal epithelial basement membrane is often thickened.
Reis Bucklers Dystrophy and Thiel-Behnke's Honey Comb
Dystrophy
It affects epithelium, Bowman's layer and anterior stroma. Clinically recurrent erosion is seen. HPE- epithelium is irregular in caliber and shows saw toothed appearance. Thick multilaminated pannus composed of alternating layers of collagen and an abnormal eosinophilic material. More eosinophilic than normal collagen resembling colour of rock candy deposits of granular dystrophy. This elevates the epithelium anterior to the plane of Bowman’s layer and Bowman’s layer is usually destroyed.
Difference- Reis Buckler's dystrophy resembles superficial variant of granular corneal dystrophykeratoepithelin forms small, sharply angulated crystalloids (Masson's trichrome positive) . Subepithelial deposits in honeycomb dystrophy are less pronounced, and show less intense positivity with Masson's trichrome.
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Primary Gelatinous Drop-like Dystrophy (Familial Subepithelial
Corneal Amyloidosis):
Focal mounds of amyloid seen in sub epithelium and superficial stroma (positive staining with Congo red). Overlying epithelium is atrophic. Bowman’s layer is usually disrupted. Amyloid is composed of the antimicrobial protein lactoferrin produced by the lacrimal gland.
Dystrophies of Corneal Stroma
Granular dystrophy: (Bucklers Type I)
It is the most benign of dystrophies of cornea. Visual loss develops late in life. Multiple white crumbs or ring shaped opacities are seen in central cornea of both eyes. Most are superficial opacities separated by clear corneal stroma, hence excellent visual acuity. HPE- mutant keratoepithelin resembles hyaline 'rock candy'. More eosinophilic, less PAS positive than surrounding normal stroma. Intense red staining with Masson’s trichrome. Granular dystrophy can recur in the graft after keratoplastythen the granular material typically accumulates in the anterior cornea underneath the epithelium.
Lattice Corneal Dystrophy Type1 (Bucklers Type II)
It is a form of amyloidosis confined to the cornea. Amyloid is a mutant form of keratoepithelin clinically. It appears as a latticework of branching relucent lines in corneal stroma. HPE shows smudgy round or oval deposits of eosinophilic amyloid material in the stroma. Lattice dystrophy can recur in the corneal graft.Amyloid first accumulates superficially underneath the epithelium and in suture tracts.
Lattice Corneal Dystrophy Type IIMeretoja Syndrome
It is a form of familial amyloidosis not related to keratoepithelin.
Amyloid deposits are located in mid-peripheral cornea and in corneal nerves. They are composed of a protein called gelsolin, which is involved in actin metabolism. Patients have amyloid neuropathy with cranial nerve palsies, dry itchy skin and mask like ' hound dog ' facies with protruding lips.
Macular Corneal Dystrophy
It is the most severe of the classic corneal stromal dystrophies. Clinically, it appears as grayish opacities with indistinct borders seen in superficial stroma. The stroma between the macules is diffusely hazy. It is a type of localized corneal mucopolysaccharidosis. Patients lack keratan sulphate in their serum and cartilage. Keratan sulphate is a major constituent of corneal ground substance. Lack of this results in abnormal hydration of the corneal stroma. So, the cornea appears thinner than normal and is hazy and poorly hydrated in systemic mucopolysaccharidosis (Hurler's disease).
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Cornea is cloudy and massively thickened
HPEcytoplasm of keratocytes and corneal endothelial cells show frothy vacuolated appearance in hematoxylin and eosin due to accumulation of insoluble non-sulfated keratan.Also seen are large extracellular deposits in the subepithelial stroma, which appear as large vesicular granules that are mildly basophilic and PAS positive. Acid mucopolysaccharide can be demonstrated by colloidal iron and Alcian blue stain.
Schnyder's Crystalline Dystrophy
It shows needle shaped polychromatic crystals of cholesterol in the anterior corneal stroma, seen as subtle pattern of stromal vacuolization in routine sections, lipid being dissolved during processing. Some patients have elevated serum lipids and xanthelasma.
Francois Neetan's Fleck Dystrophy
It is an incidental clinical findingunilateral. Visual acuity is not affected. Keratinocytes are swollen and contain mucin and lipid.
Congenital Hereditary Stromal Dystrophy
Shows bilateral corneal clouding. Cornea is of normal thickness but its collagen fibres are one half of normal diameter.
Pre-Descemet's dystrophy shows fine flour like opacities called cornea farinata. It is thought to be an age related degenerative change.
In deep filiform dystrophy, keratocytes are enlarged and contain fat and phospholipid inclusions.
Corneal Edema, Bullous Keratopathy and Endothelial
Dystrophies
Corneal edema can occur in corneas with damaged or dysfunctional endothelium (endothelial decompensation) due to aphakia, pseudophakic bullous keratopathy, and corneal graft failure. Primary endothelial disease can also cause corneal edema. Endothelial dystrophies include Fuch's dystrophy (common), congenital hereditary endothelial dystrophy and posterior polymorphous dystrophy.
HPE of edematous cornea- Cornea is thickened with partial obliteration of artifactitious intralamellar stromal clefts. Lamellar margins are indistinct. edematous stroma is pale and has frothy appearance- "cotton candy". As secondary epithelial edema develops basal cells have pale edematous appearance. Fluid accumulates in intercellular spaces and beneath the epithelium, forming focal bullous areas of epithelial detachment called bullous keratopathy.
A degenerative pannus is found in many corneas with chronic edema and bullous keratopathy. It is seen as opaque layers of connective tissue between base of the epithelium and Bowman's layer, which is intact.
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Fuch's Endothelial Dystrophy
It is the most common corneal dystrophy and presents during adult life with corneal edema and bullous keratopathy. It is due to primary defect in the corneal endothelium. Descemet's membrane is typically thickened and studded with anvil or mushroom shaped guttate excrescences of abnormal basement membrane material produced by dystrophic endothelial cells.
HPE- central cornea shows guttae that have been buried by a newly elaborated posterior layer of Descemet's membrane. Descemet's membrane shows thickening and multilamination. Rarely, Descemet's membrane lacks guttate excrescences and appears diffusely thickened. Endothelium is atrophic. Moderate number of corneal endothelial cells usually persist. Cytoplasm of the residual endothelium contain round granules of melanin pigment from iris pigment epithelium.
Pseudophakic Bullous Keratopathy: Latrogenic Disease
It is due to direct or delayed endothelial damage associated with cataract surgery and IOL implantation. It is the most common cause of corneal transplantation in recent years.
HPE- Descemet's membrane is not thickened and is regular in caliber. No guttate excrescences. Endothelium is severely atrophic or totally absent. Bullous keratopathy may be severe and some cases show total epithelial desquamation. Degenerative pannus formation is not so frequent as pseudophakic bullous keratopathy has a more acute course.
Identical picture of corneal edema is seen in failed corneal transplants. Eosinophilic retrocorneal fibrous membrane is found on the posterior surface of Descemet's membrane.
Congenital Hereditary Endothelial Dystrophy: (CHED)
It presents as massive corneal edema. Endothelium may be normal or atrophic. Massive thickening of Descemet's membrane seen in some cases.
Posterior Polymorphous Dystrophy
There is no corneal edema.Endothelium is hypercellular and shows multilayering. The abnormal endothelial cells express surface epithelial cytokeratins.
DEGENERATIONS OF CORNEA
Variety of secondary corneal degradations initiated by inflammatory, traumatic (accidental or surgical), metabolic or aging processes occur. Degenerations are classified as -
Epithelial and subepithelial degeneration. Stromal degeneration.
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Epithelial and subepithelial degeneration
1.Keratoconjunctivitis sicca and xerophthalmia.
2.Exposure keratopathy and Dellen.
3.Neurotrophic keratopathy.
4.Pterygium.
5.Band keratopathy.
6.Degenerative and inflammatory pannus.
7.Salzmann's nodular degeneration.
8.Marginal degeneration.
Stromal degeneration
1.Keratoconus.
2.Acute keratoconus (hydrops) .
3.Pellucid marginal corneal degeneration.
4.Polymorphic amyloid degeneration.
5.Secondary amyloid degeneration.
6.Deep or posterior crocodile shagreen.
Keratoconjunctivitis sicca (Sjogren's syndrome) and xerophthalmia (Severe vitamin A deficiency) - Due to deficient or abnormal tear production. There is corneal drying, superficial punctate keratopathy and filamentary keratitis composed of strands of detached corneal epithelium and mucous.
There is epithelial thickening and opacification, accompanied by secondary subepithelial pannus and stromal haze or scar, leading to thinning and perforation. In late cases, epithelium shows histologic changes characterized by irregular acanthosis and epidermalisation. May be associated with subepithelial vascularisation, fibrosis, loss of Bowman's layer and inflammatory cell infiltration. When secondary infection occurs, partial or full thickness ulceration may be seen.
Exposure Keratopathy and Dellen
It is due to incomplete lid closure due to facial palsy, proptosis, eyelid deformity or coma due to incomplete lid closure, exposed epithelium becomes dry and undergoes punctate degeneration in interpalpebral zone. In severe cases larger areas of epithelium breakdown, leading to secondary infection with or without ulceration.
Dellen - Epithelium overlying a thinned area of dehydrated stroma exhibits punctate irregularities and results in depression of the surface called dellen.
Neurotrophic Keratopathy (Trophic Ulcer)
It is due to lesion of the trigeminal nerve that interrupts sensation and trophic impulses to the epithelial cells. There is persistent epithelial edema, vesicle formation and erosion. Stroma is diffusely hazy. Late vascularisation may also develop. Following breakdown of epithelium, healing is slowed. If untreated, secondary bacterial ulceration can occur.
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HPEIn late or secondarily infected cases there is stromal scarring, vascularisation and acanthotic epithelial changes.
Calcific Band Keratopathy
It is a superficial opacity that extends across the part of cornea exposed in interpalpebral fissure. It is caused by dystrophic calcification of Bowman's membrane and the anterior stroma. It is seen in iridocyclitis, long-standing glaucoma, phthisis bulbi, vitamin D excess and hypercalcemia.
In early cases Bowman's layer is of irregular thickness with stippled deposition of calcium salts in the basement membrane of overlying epithelium, Bowman's layer and subjacent superficial stroma. In advanced cases, there is calcification and fragmentation of Bowman's layer. Subepithelial fibrosis may be seen.
Chronic actinic keratopathy (spheroidal keratopathy, Labrador keratopathy, Climatic droplet keratopathy):
It shows multiple spherules of yellow hyaline material in the anterior cornea. HPE shows drop like deposits of varying sizes seen as amorphous hyaline material that stains light gray or amphophilic with hematoxylin and eosin stain. The deposits stain intensely with elastic tissue stains and are considered as a form of elastic degeneration of the collagen.
Degenerative and Inflammatory Pannus
Term pannus is applied to a flat superficial scar of anterior cornea. There are two typesinflammatory and degenerative.
Inflammatory pannus occurs in trachoma. Here, Bowman's layer is destroyed and replaced by vascularised connective tissue with appreciable round cell infiltration.
Degenerative pannus occurs in corneas with chronic edema and bullous keratopathy. There is subepithelial fibrovascular membrane with minimal inflammatory cells and preservation of Bowman's layer. The vascular connective tissue of the pannus arises from the conjunctiva.
Salzmann's Nodular Degeneration
It is a secondary degenerative process of unknown cause. Corneal epithelium shows elevated white mounds of dense collagenous connective tissue. HPEresembles a massive focal pannus. There are mounds of relatively acellular hyaline connective tissue that elevate the corneal epithelium anterior to the plane of Bowman's membrane which may be destroyed.
Marginal Degeneration
It begins in upper cornea adjacent to accompanying arcus senilis. Degeneration originates in the stroma. Initially, Bowman's layer and the peripheral superficial lamellae undergo fibrillar degeneration followed by thinning and partial
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replacement with vascularised connective tissue. Deep lamellae eventually degenerate and only a thin fibrovascular layer separates the outwardly bulging Descemet's membrane from the epithelium.
Lipid Keratopathy
Lipid deposition occurs in the peripheral corneal stroma in arcus senilis. If patient is below 40 years, it can signify a hyperlipemic state. It is a secondary phenomenon caused by lipid deposition in a heavily vascularised stroma.
Corneal epithelial keratinisation and epidermalisation
It is due to deficient tear production or mucous secretion. It occurs in severe vitamin A deficiency. Dry white spots are seen at the limbus (Bitot’s spots) , which may contain colonies of Corynebacterium xerosis.
HPEshows irregular acanthosis of the epithelium, hyperkeratosis and formation of discrete ridges. Bowman's layer is destroyed and replaced by subepithelial fibrovascular tissue with mild chronic inflammatory cell infiltration (Inflammatory pannus).
Keratoconus
It is a bilateral degenerative disorder. There is progressive thinning or ectasia of the central stroma that imparts a conical configuration to the cornea.
HPEsectioned cornea assumes an irregular wavy configuration. There is a central or apical thinning of the stroma (less than 1/10 th of normal thickness). Characteristic dehiscences in Bowman's membrane are common and appear wavy in configuration. Corneal epithelium usually is intact and irregular in caliber, with areas of thinning and compensatory hyperplasia. Descemet’s membrane is thin. Endothelium is well preserved.
Acute Keratoconus (hydrops)
In advanced cases, rupture of Descemet's membrane and the endothelium results in severe stromal and epithelial edema with rapid onset of clouding of the cornea.
HPEshows elastic retraction of the free ends of Descemet’s membrane, which coils on itself and is thrown into folds.
Pellucid Degeneration of Cornea
It resembles keratoconus histopathologically, but is located in the periphery of the cornea.
Polymorphic Amyloid Degeneration
It resembles lattice dystrophy clinically and microscopically. HPECorneal epithelium and Bowman's layer are normal. Small amyloid deposits are present in the stroma.
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Degeneration of Conjunctiva
Chronic irritation due to exposure to ultra violet actinic exposure damages the stromal connective tissue of the bulbar conjunctiva, which is exposed in the interpalpebral fissure and results in pinguecula and pterygium.
Pinguecula- it is a localized yellowish grey elevated mass close to the limbus on either side of cornea in the interpalpebral portion of bulbar conjunctiva.
Pterygium is similar in appearance and seen more often nasally and involves cornea also.
HPEboth lesions show similar features. Overlying epithelium can be thin from atrophy or thickened by reactive secondary changes of hyperplasia, hyperkeratosis, acanthosis, dyskeratosis or even dysplasia. Subepithelium shows accumulation of amorphous, eosinophilic staining, hyalinized or granular appearing material resembling degenerated collagen interspersed with coiled or fragmented fibres resembling abnormal elastic tissue (elastoid or elastotic degeneration). Stromal fibrocytes are increased in number.
Older lesions also show aggregates of proteinaceous substance, acid mucopolysaccharide and calcific concretions.
Conjunctival Amyloidosis
It is a localized phenomenon seen in healthy adults without systemic amyloidosis. It can involve any part of conjunctiva. Subepithelial amyloid can form circumscribed, polypoidal, yellowish waxy nodules on the epibulbar surface or diffusely infiltrate the substantia propria.
HPEshows relatively acellular amorphous deposits of eosinophilic hyaline material. It can be confirmed by special stains for amyloid.
RETINAL DEGENERATIONS
Peripheral Retinal Degenerations
Peripheral chorioretinal degeneration (cobble stone or paving stone degeneration):
It is seen in more than 25% of individuals above 20 years. It is more common in myopes. Lesion appears as yellow white patches of chorioretinal atrophy. Borders are sharply demarcated, scalloped and often pigmented. Pigmentation is due to hyperplasia of adjacent RPE. Patches appear white because the overlying sclera is bared by the severe atrophy of RPE and choriocapillaries.
HPEOuter retina is firmly adherent and welded to the inner surface of Bruch's membrane, which is devoid of RPE. Rods and cones are absent in the area of chorioretinal adhesions and replaced by gliosis. Underlying choriocapillaris is atrophic.
Peripheral microcystoid degeneration:
It occurs in two formstypical and reticular.
In typical form there is a stippled pattern that corresponds to an array of interconnecting channels or lacunae in the peripheral retina just posterior to
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the ora serrata. HPEOuter plexiform and inner nuclear layer contains multiple cystoid spaces called BlessigIwanoff cysts, which are filled with hyaluronic acid and are separated by residual pillars of Muller cells. With time the spaces may spread vertically to involve the retinal layers above and below.
Reticular cystoid degeneration is seen posterior to typical cystoid degeneration and principally involves the ganglion cell layer and the nerve fibre layer. It may be the cause of reticular retinoschisis, where the split in the retina occurs in the nerve fibre layer.
Retinoschisis
There is splitting of the layers of sensory retina. Cystoid degeneration is called schisis, when the spaces measure more than 1.5 mm linearly. Typical degenerative schisis forms from typical cystoid degeneration involving the outer plexiform and inner nuclear layers.
Reticular schisis forms from reticular degeneration. With time the inner layer consists of only the internal limiting membrane and retinal vessels. This inner layer may form a large bullous separation.
Age Related Macular Degeneration (ARMD)
It causes loss of central vision because it involves the fovea. Peripheral vision is retained. Manifestations may be atrophic (dry) or exudative (wet) , both are part of the clinical and pathologic spectrum and hence seen in the same patient.
Dry (atrophic) macular degeneration is characterized by atrophy and death of the subfoveal RPE. This leads to photoreceptor degeneration and outer retinal atrophy. Bruch's membrane thickens with age and become disorganized. HPEthere is increased basophilia of Bruch's membrane due to calcification and a progressive increase in lipid deposition. With increased age wide banded collagen is also deposited in Bruch’s membrane.
Drusen are the initial clinical findings in ARMD. They are clinical markers for sick RPE and consist of mounds or accretions of abnormal extracellular matrix material that form on the inner surface of Bruch's membrane. They are probably synthesized by the RPE.
There are two types of drusen—hard and soft. Hard or cuticular drusen are discrete, round or globular mounds of homogenous deeply PAS positive hyaline material with thinning of the overlying RPE. They are found beneath the basement membrane of the RPE and are formed due to apoptosis of the photoreceptors after a variety of injuries.
Soft drusen have less well defined boundaries. They are identical to small retinal pigment epithelial detachments. The involved area is larger and more irregular than that of a hard drusen and the material appears granular and less uniform. There is diffuse deposition of material beneath the pigment epithelium called basal laminar deposits, which adhere loosely to the Bruch's membrane predisposing to RPE detachments, tears, neovascularisation and scarring.
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With time the retinal pigment epithelial cells overlying drusen atrophy and the drusen become fibrotic and sometimes calcify.
Window defects—correspond to the thinned pigment epithelium over the apex of hard drusen in ARMD. They may be a precursor to areolar atrophy.
Areolar Atrophy
It is a "dry" type of macular degeneration. Histologically, there is loss of photoreceptors and the RPE, with adhesions of the outer plexiform layer against Bruch’s membrane.
Serous Retinal Pigment Epithelial Detachment
It is actually a separation between the split layers of Bruch's membrane and results from enlargement and coalescence of soft drusen.
Subretinal neovascularisation and disciform scarring can result fromARMD, myopia, angioid streaks and ocular histoplasmosis.
Disciform degeneration- There is loss of photoreceptors and only few nuclei remain in the outer nuclear layer. There is proliferation of pigment epithelium with retention of pigmentation. Bruch’s membrane is split; the outer portion overlies intact choriocapillaris. Blood vessels are seen interior to this portion of bruch's membrane within the disciform scar. Other degenerative changes include cystoid degeneration, lamellar and full thickness macular holes.
Subretinal neovascular membrane characterizes the exudative type ofARMD. Untreated subretinal neovascularisation occasionally undergoes spontaneous involution. More often the vessels leak or bleed forming serous or hemorrhagic detachments of the RPE.
Fibrous disciform scar formation, the end stage of exudative ARMD, usually results from the organization of hemorrhagic RPE detachment. HPE shows mature scars composed of mounds of dense collagenous connective tissue on the inner surface of Bruch’s membrane. The collagenous scar usually contains vessels and aggregates of RPE cells. Massive fibrous dysplasia of RPE is seen in eyes with chronic retinal detachment. Bone formation (osseous metaplasia of the RPE) is almost always the rule in phthisical eyes. Subretinal neovascular membrane also complicates other conditions such as angioid streaks.
Angioid Streaks
They are idiopathic in 50% of patients. It may be associated with Pseudoxanthoma elasticum, sickle cell anemia, other hemolytic anemias and Paget’s disease. Angioid streaks resemble blood vessels. It appears as irregular reddish-brown crack like lesions radiating outward from the optic disc.
HPEthe streaks correspond to discontinuities in Bruch's membrane, which is thickened and calcified at the level of elastic layer. Calcification causes the increased brittleness of Bruch’s membrane, which predisposes to subretinal neovascularisation.