External Disease and Cornea
Corneal
Dystrophies (anatomic classification)
- Epithelial
Dystrophies
- Stromal
Dystrophies
- Endothelial
Corneal epithelial basement membrane dystrophy
(map-dot-fingerprint or Cogan microcystic
dystrophy)
Most common dystrophy, 6-18% of
the population. Possibly dominant inheritance
with incomplete penetrance, often sporadic. Women and >50 yrs old more common.
- Pathogenesis:
- abnormality of epithelial
turnover, maturation and production of basement membranes.
- Thickened basement membrane that extends into
epithelium.
- Epithelial cells missing hemidesmosomes.
- Clinical
findings:
- map lines, dots or
microcysts, fingerprint lines.
- Variable findings that change with time.
- Recurrent corneal erosions
- Maps and fingerprints are intraepithelial basement
membranes
- Dots are senescent epithelial cells trapped in
epithelium unable to exfoliate
- Symptoms:
- Related to recurrent epithelial erosions (in 10%) and
transient blurred vision.
- Management:
- 5% sodium chloride or other lubricating ointment,
lubricating drops,
- epithelial scraping,
patching, bandage contact lens,
- anterior stromal
puncture.
- PTK into anterior 2-4 microns of Bowman's.
Meesmann dystrophy (juvenile
epithelial dystrophy)
Autosomal Dominant, bilateral, occurs very
early in life
- Pathogenesis:
- Thickened epithelium and a multilaminar,
thickened epithelial basement membrane.
- epithelial cells contain
an electron-dense, fibrillogranular unknown
substance ("pecular substance") and
glycogen.
- Clinical
findings:
- Tiny intraepitheilial vessicles (cystic spaces) extending out to the
limbus.
- More numerous in the interpalpebral
area. Surrounding epithelium is clear.
- Cornea slightly thinned with less sensation.
- Symptoms:
- Mild irritation and slight decrease in acuity
- Management:
- Most need no treatment. bandage
contact lenses, rarely superficial PTK
Reis-Bücklers dystrophy
Autosomal Dominant, Chromosome 5q31 (same
region as Granular, Avellino and Lattice)
affects Bowman's layer, appears in first few years of life, progressive
- Pathogenesis
- Mutation in ßig-h3, human tranforming
growth factor, responsible for formation of keratoepithelin
- material that
accumulates is unknown
- Deep epithelium degenerates but basement membrane is
spared.
- Bowman's layer is disrupted or absent and replaced by fibrocellular tissue in a curly or sawtooth pattern that corresponds to areas of subepithelial opacification.
- Electron Microscopy: "curly fibers" at level
of Bowman's layer
- Clinical
findings
- geographic or honeycomb,
gray-white reticular opacification
- central cornea more
affected
- posterior cornea normal
- surface irregularity
with recurrent erosions
- Symptoms
- Painful, recurrent epithelial erosions in first or
second decade
- Vision reduced by anterior stromal scarring and edema
- Laboratory
evaluation: EM appearance
- Type I- rod shaped bodies
- Type II (Thiel-Behnke
dystrophy)- curly fibers and linkage to
10q24 gene, more typical honeycomb appearance
Granular dystrophy
Autosomal Dominant, Chromosome 5q31 (along
with Avellino, Lattice, Reis-Bücklers),
- Pathogenesis
- collection of hyaline
material that stains red with Masson trichrome
stain or H&E
- deposits are noncollageonus protein
- Clinical
Findings: Three forms
- Type I: most frequent
(a.k.a. Groenouw dystrophy type I), early
onset, crumb-like opacities that broaden into a disciform
appearance by teens, do not extend to limbus but can extend through
breaks in Bowman's, vision 20/200 after age 40
- Type II: second decade
of life, fewer, larger ring or disc shaped deposits, intervening clear
areas, vision 20/70.
- Type III: more
superficial, presents with erosions in infancy, granular deposits in
anterior stroma or Bowman's, resembles Reis-Bücklers
dystrophy
- Management
- Treat erosions: bandage contact lens, superficial
keratectomy, PTK. PK has good prognosis, recurrence in the graft after
many years as fine subepithelial opacities.
Avellino dystrophy- (Granular-Lattice
dystrophy)
Traced from a family in Avellino Italy. Autosomal
Dominant, Chromosome 5q31. Pathogenesis
- Same mutation as lattice
dystrophy in ßig-h3.
- Have both hyaline and amyloid deposits
in stoma.
- Clinical
Findings
- Lattice and granular lesions coexist.
- Older patients have anterior stomal
haze.
- Management
- Treat erosions: bandage contact lens, superficial
keratectomy, PTK.
- PK has good prognosis, recurrence in the graft after
many years as fine subepithelial opacities.
Lattice dystrophy
Autosomal Dominant, variable expression of
glass-like branching lines in stroma
- Pathogenesis
- Genetic defect in the ßig-h3 gene responsible for the
formation of keratoepithelin but not in one of
the 14 known amyloid-associated genes
- Amyloid deposits in subepithelial area causing poor epithelial-stromal
adhesions.
- Congo red dye stains amyloid
orange-red
- Dichroism and birefringence.
- Clinical
Findings
- Classic branching glass-like branching lines but
spectrum of corneal changes is broad.
- Stroma can take on a
ground-glass appearance (hazy intervening stroma)
- Lesions appear early in life with common recurrent
epithelial erosions, vision can be affected
- Three types:
- Type I: (Biber-Haab-Dimmer) classic
Lattice dystrophy, onset 1st decade of life, no
systemic amyloid deposition. Type AA amyloid.
- Type II: (Meretoja syndrome) lattice dystromphy
with coexisting systemic amyloidosis, manifests around age 20, mask
face, blepharochalasis, pendulous ears,
cranial and perepherial nerve palsies, dry lax
skin. Mutation in Chromosome 9q34. Neither type AA or AP amyloid
- Type III: Autosomal Recessive. Midstromal deposits. Symptoms 5-7th decade of life. Recurrent
erosions uncommon. Type IIIa: Autosomal
Dominant, recurrent erosions common, only in whites.
- Management
- Treat recurrent erosions: BCL, superficial
keratectomy, PTK
- PK has recurrence in 2-12 years (more frequent than
granular or macular)
Macular dystrophy
Autosomal Recessive, least common, involves
entire cornea, decrease in vision at an earlier age
- Pathogenesis
- Glycosaminoglycan (acid mucopolysaccharide: Keratin sulfate) deposits
accumulate in endoplasmic reticulum of keratocytes
and endothelium
- Stain with colloidal iron or Alcian Blue stains
- Linked to chromosome 16q22
- Clinical
Findings
- Cornea begins to cloud age 3-9
- Focal gray-white superficial stromal opacities that
progress to involve full thickness
- Extends to corneal perephery
- Intervening stoma diffusely cloudy
- Corneal guttatae
- Erosions less common
- Vision loss common
- Two types: based on
biochemical differences, similar clinical picture
- Type I: lack
antigenic keratan sulfate in cornea, serum and
cartilage.
- Type II: synthesize
normal keratan sulfate and dermatan
sulfate but at 30% normal levels and chains are 40% shorter than normal.
- Laboratory
Evaluation
- ELISA can measure keratin sulfate and identify macular
dystrophy even in preclinical years or carriers
- Management
- Treate recurrent
erosions with BCL, superficial keratectomy, PTK
- PK good prognosis, recurrences in graft occur.
Gelatinous droplike dystrophy (primary
familial amyloidosis)
- Autosomal
Recessive, Chromosome 1p
- Typical Amyloid
as subepithelial deposits
- Source of
amyloid may be basal epithelial layer
- Most reports in
Japanese literature
- Onset 1st
decade, resembles band keratopathy at first
- Advanced cases
develop protruding, mulberry-like subepithelial
deposits
- Manage similar
to Lattice dystrophy
- Recurrence high
in PK
Schnyder central crystalline dystrophy
Autosomal Dominant, Chromosome 1p36-p34.1,
appears in 1st year of life
- Pathogenesis
- Deposits of unesterfied
cholesterol and neutral fats
- Oil red O stains the
neutral fat red
- Cholesterol and other fats are dissolved
- EM shows accumulation in epithelium, Bowman's and stroma
- Clinical
findings: any combination of the following
·
Minute yellow-white crystals
(cholesterol)
·
Diffuse stromal haze
·
Dense corneal arcus
·
Type I limbal girdle of Vogt
·
Xanthalasma
·
Central opacities accumulate just
underneath Bowman's layer, often in doughnut-like or wreath configuration
·
Epithelium usually uninvolved
clinically
·
Cornea does not vascularize
- Laboratory
evaluation:
- fasting lipid profile
for possible hyperlipoproteinemia type II-a,
III, or IV, or hyperlipidemia
- 50% have elevated serum cholesterol
- Management
- Rare vision loss to the point of needing PK,
recurrence in PK does occur
- PTK is used for reduced vision
- Manage lipids
Fleck dystrophy
Probably Autosomal Dominant, may be
congenital or occurs very early in life, can show extreme asymmetry
- Pathogenesis
- Keratocytes contain excess
glycosaminoglycan which stains with Alcian
blue and colloidal iron
- Keratocytes also contain lipids
staining with Sudan black B and oil red O
- Clinical
Findings
- Discrete flat, gray-white dandrufflike
(sometimes ring shaped) opacities throughout stroma
to its periphery.
- Only stroma involved.
- Symptoms minimal. Vision usually not reduced
- Possible associations: decreased corneal sensation,
limbal dermoid, keratoconus,
central cloudy dystrophy,
punctate cortical lens changes, pseudoxanthoma elasticum, atopy
Central Cloudy dystrophy
(of François)
Autosomal Dominant, non
or slowly progressive
- Pathogenesis
- unknown cause
- deep stromal layers
have sawtooth folds
- Clinical
Findings
- Opacity most dense centrally and posteriorly and fades
anteriorly and peripherally
- Multiple nebulous, polygonal gray areas separated by cracklike intervening clear zones.
- Vision usually not reduced
- Differs from posterior crocodile shagreen
because of it's strong autosomal dominant inheritance and haze extending
anteriorly in cornea
- Management
Fuchs endothelial dystophy
Variable
autosomal dominant tranmission, may be sporadic,
onset after 50 years, female preponderance
- Pathogenesis
- Primary
dysfunction of endothelial cells causing corneal swelling, deposition of
collagen and extracellular matrix in Decemet's
membrane (may be cause or effect)
- Reduction in
number of ATPase Na+, K+ pumps and pump function
- Clinical Findings
- Variable severity
- Corneal guttata first evident centrally then peripherially with loss of endothelial cells
- Thickened Decemet's membrane and folds secondary to stromal
edema
- Increased
endothelial pigmentation
- Central corneal
thickness may approach 1mm (normal 0.52 to 0.56 mm)
- Epithelial
edema develops, leading to microcystic edema
and bullae
- Longstanding
edema can lead to supepithelial fibrosis (degenerative pannus)
- Symptoms
- Decreased
vision and pain from ruptured bullae
- Worse upon
awakening because of less surface evaporation while sleeping
- Painful
episodes may subside following subepithelial
fibrosis
- Laboratory Evaluation
- Specular
microscopy to follow endothelial cell counts
- Corneal pachymetry to follow endothelial cell function
- Cell count
<1000/mm2 or central corneal thickness >650 microns
suggest the possibility the cornea will decompensate with surgery
- Management
- Goals: Reduce
corneal edema and relieve pain
- Sodium chloride
drops and ointment (5%)
- Lower IOP,
- Lubricating
drops
- Soft bandage
contact lens
- Conjunctival flap
- PK before
entire cornea becomes edematous- PK has good prognosis
Posterior polymorphous dystrophy (PPMD)
Autosomal dominant or
recessive, slowly progressive, variable clinical spectrum, often
asymmetric, linked to 20q11
- Pathogenesis
- abnormal multilayered
endothelial cells that have; microvilli, stain for keratin, grow rapidly
and easily in cell culture, have intercellular desmosomes and have
proliferative tendencies
- similar cell changes
in ICE syndomes
- Clinical
Findings
- Posterior corneal surface; isolated grouped vesicles,
geographic-shaped gray lesions, broad band with scallop edges
- stromal edema, corectopia, broad iridocorneal
adhesions
- both angle closure
and open-angle glaucoma may occur- 14% have high IOP
- Laboratory
evaluation
- Specular microscopy: vesicles and bands of endothelium
- Management
- most are stable and
asymptomatic
- corneal edema: 5% NaCl drops or ointment
- localized corneal edema:
stromal puncture to induce supepithelial pannus
- manage glaucoma
- corneal transplant for
intractable corneal edema- prognosis related to PAS and glaucoma, graft
reoccurrence possible
Congenital Heriditary Endothelial dystrophy
- Two forms:
- Autosomal recessive (CHED 2): presents at birth, remains stationary, nystagmus, blue
corneas 2-3 times thicker than normal with ground glass appearance, no
tearing or photophobia, diffuse non-bullous epithelial edema, no guttate
- Autosomal dominant (CHED 1): presents 1st-2nd decade, variable expressivity, abnormal differentiation of neural crest ectoderm.
Associated with axial myopia. No other consistent systemic associations.
(Chromosome 20q11.2)
Episcleritis
- Collagen-vascular
and other inflammatory diseases
- *Rheumatoid arthritis
- Inflammatory bowel disease
- *Crohn's disease
- Ulcerative colitis
- Psoriatic arthritis
- Systemic lupus erythematosus
- Reiter's syndrome
- Relapsing polychondritis
- Ankylosing spondylitis
- Vasculitic diseases
- Polyarteritis nodosa
- Temporal arteritis
- Cogan's syndrome
- Churg-Strauss
syndrome
- Wegener's granulomatosis
- Behçet's disease
- Dermatologic
diseases
- Metabolic
diseases
- *Atopy
- Blood dyscrasias
- Foreign body
- Vegetable matter
- Animal matter (insect hairs)
- Mineral matter (suture, talc, stones)
- Chemical injury
- Infectious
- Bacteria
- Mycobacteria
- Atypical mycobacterial disease
- Tuberculosis
- Hansen's disease
- Spirochetes
- Chlamydia
- Actinomyces
- Fungi
- Viruses
- *Herpes zoster
- Herpes simplex
- Mumps
- Parasites
- 1. Protozoa
- Acanthamoeba
- Toxoplasmosis
- Helminths
Adapted from Foster CS, Sainz de la Maza M: The sclera, New York, 1994, Springer-Verlag.
- Antinuclear
antibody
- Serum uric acid
- Erythrocyte
sedimentation rate
- Complete blood
count with differential
- VDRL-FTA
- Urinalysis
- PPD
- Chest x-ray
Ocular Surface
Disorders
Dermatoses
Conjunctival
vascular abnormalities
Tear deficiencies
Limbal stem-cell dysfunction
Nutritional/physiologic
Structural/exogenous
Dermatoses affecting Ocular Surface
Seborrheic blepharitis
Chalazion
Hordeolum
Rosacea
Sarcoidosis
Desquamating conditions
Ectodermal dysplasia
Xeroderma pigmentosum
Conjuctival vascular abnormalities
Hereditary hemorrhagic telangiectasia
Lymphangiectasia
Tear deficiencies
Keratoconjunctivitis sicca (Dry eye)
Meibomian gland dysfunction (lipid)
Aqueous tear deficiency
Mucin tear deficiency
Nutritional & physiologic
disorders of ocular surface
Vitamin A deficiency
Vitamin C deficiency
Neurotropic keratopathy
Structural & exogenous
disorders of ocular surface
Exposure keratopathy
Floppy eyelid syndrome
Superior limbic keratoconjunctivitis
(SLK)
Recurrent corneal erosion
Persistent epithelial defect
Trichiasis & distichiasis
Factitious conjunctivitis
Delle
Contact lens wear
Superior limbic keratoconjunctivitis (SLK)
- Pathogenesis
- unknown: increased
friction between superior bulbar and tarsal conjunctiva
- Some have history of thyroid dysfunction and conjunctival edema
- Clinical
presentation
- chronic, recurrent
ocular irritation and redness, often bilateral but asymmetric
- adult women: 20-70
years
- recurrs over 1-10 year
- usually resolves
spontaneously
- Signs
- fine papillary
superior tarsal conjunctiva
- injection and thickening
of superior bulbar conjunctiva with fine punctate staining
- hypertropy of superior limbus
- superior corneal
filaments
- associations: aqueous tear
deficiency and blepharospasm
- Laboratory
evaluation- clinical signs usually suffice to
make diagnosis
- scraping or impression
cytology show pyknosis, "snake
nuclei", increased epithelial cytoplasm/nucleus ratio, loss of
goblet cells, keratinization
- Thyroid function tests: T3, T4, TSH
- Management
- chemical cauterization
of superior bulbar conjunctiva: 0.5-1.0% silver nitrate solution in wax
ampoules
- large diameter
bandage contact lens
- topical vitamin A
ointment (0.1% transretinoic acid)
- thermocautierization of superior bulbar conjunctiva
- resection of superior
bulbar conjunctiva
Organisms that can Invade an Intact Cornea
- Nisseria
gonorrhea
- Corynebacterium
diphtheria
- Listeria monocytogenes
- Haemophilus aegyptius