Diseases of the Cornea

MT 2

Which nerve supplies the subepithlelial and stromal nerve plexus of the cornea?

First division (ophthalmic) of trigeminal nerve

Corneal diameter

• Vertical = 11.5mm

• Horizontal = 12mm

Where does the cornea get its nutrients?

It’s avascular, so the aqueous humor and tear film

Average central corneal thickness =

540 micrometers

5 Layers of Cornea

• Epithelium: stratified squamous

  • non-keratinized

  • basal cells, wing cells, squamous surface cels

  • microplica & microvilli that assist in adhesion of the mucin layer of the tears

  • Corneal stem cells are located at the limbus

  • Will regenerate following trauma

• Bowman layer: acellular superficial layer of stroma composed of collagen

• Stroma: makes up 90% of the corneal thickness

  • Composed of regularly orientated layers of collagen fibrils = clear

  • Will not regenerate following trauma

• Descemet membrane: composed of fine latticework of collagen that is distinct from the stroma

  • Has two bands, one develops in utero and one that is laid throughout life and serves as basement membrane for endothelium

• Endothelium: monolayer of hexagonal cells that are responsible for deturgescence

Treatment for Recurrent Corneal Erosions (RCE)

• Debridement: surgical intervention to remove irregular epithelium on active RCE

• Phototherapeutic keratectomy-done with excimer laser

• Stromal puncture: causes scar tissue which will anchor the epithelium to stroma

• Bandage contact lens

Meesmann epithelial dystrophy (juvenile hereditary epithelial dystrophy)

• rare

• autosomal dominant mutation in gene responsible for producing epithelial keratin

• Onset: first year of life

• Symptoms: asymptomatic or blurry vision, glare, light sensitivity, discomfort (if cysts rupture onto epithelial surface-which does not occur until adolescence or adulthood)

• Presentation: intraepithelial cysts and vesicles

  • small & filled with degenerated epithelial cell products

  • Cysts will extend towards the limbus but will be concentrated centrally and interpalpebrally

  • clear spaces surround the cysts

• Complications: recurrent corneal erosions

• Treatment:

  • asymptomatic = no tx

  • lubrication = for irritation if cyst rupture

  • debridement for RCE

  • Lamellar keratoplasty: if significant corneal opacification occurs and leads to reduced visual acuity (rare)

Meesmann epithelial dystrophy (juvenile hereditary epithelial dystrophy) Treatment

• asymptomatic = no tx

• lubrication = for irritation if cyst rupture

• debridement for RCE

  • other RCE tx

• Lamellar keratoplasty: if significant corneal opacification occurs and leads to reduced visual acuity (rare)

Reis-Bückler dystrophy

• epithelial-stromal dystrophy

• bilateral

• onset: 1st decade, but not born with corneal signs

• Bowman layer is replaced by connective tissue bands

• Symptoms: more symptomatic than epithelial dystrophies

  • Visual complaints: blurred vision, photophobia and diplopia

  • Foreign body sensation and pain often due to RCE

• Presentation: grey-white geographic subepithelial opacities

  • more dense central

  • denser w/ age and for a reticular pattern (cause stromal haze)

  • rod-like appearance

  • Corneal sensitivity will be reduced*

  • inc. corneal thickness

  • irregular astigmatism

How do you differentiate btwn Reis-Bückler dystrophy and Thiel-Behnke dystrophy?

electron microscopy

Theil-Behnke Dystrophy

• epithelial-stromal dystrophy

• bilateral

• onset: 1st decade, but not born with corneal signs

• Symptoms: more symptomatic than epithelial dystrophies

  • Visual complaints: blurred vision, photophobia and diplopia

  • Foreign body sensation and pain often due to RCE

• less severe then Reis-Bückler

• Presentation: curly fibers on electron microscopy

  • Predominantly affects the central cornea

  • Opacities will be less defined when compared to Reis-Bückler

  • Opacities will develop in a ring or honeycomb like pattern

  • Will not present with corneal irregularities or decrease corneal sensation

Reis-Bückler dystrophy and Thiel-Behnke dystrophy Complications

• Recurrent corneal erosions in early childhood

• Corneal opacifications (worse with Reis-Buckler)

Reis-Bückler dystrophy and Thiel-Behnke dystrophy Treatment

• observation

• Recurrent corneal erosion treatment: hypertonic salt solution or debridement

• Lamellar keratoplasty with significant reduced visual acuity

Lattice dystrophy

• Most common of the epithelial-stromal dystrophies

• autosomal dominant

• Onset: first decade

• Assoc. with systemic amyloidosis

• Pathophysiology: amyloid deposits accumulate between epithelial basement membrane and Bowman layer and the anterior stroma

• Symptoms: blurred vision and pain with recurrent corneal erosions

• Presentation: amyloid deposition in anterior stroma

  • Corneal deposits will be refractile dots that coalesce to form linear lines (makes lattice)

  • Over time corneal deposits will be surrounded by haze that will eventually fibrous = opacification

  • Affects central cornea

  • Reduced corneal sensitivity

• Complications: recurrent corneal erosions, blurred vision (due to haze)

• Treatment:

  • observation

  • RCE tx

  • lamellar keratoplasty

Granular dystrophy

• Onset: first to second decade

  • 1st = granular 1

  • 2nd = granular 2

• Pathophysiology: hyaline deposition

• Two types: granular 1 and granular 2

Granular 1 Dystrophy

• Symptoms:

  • asymptomatic early on

  • Eventually develop blurred vision, photophobia, glare and pain with RCE

• Presentation: small well defined hyaline deposits (crumb like) in the anterior stroma

  • There will be a clear space in between the deposits; deposits become more confluent w/ progression

  • Opacities will extend posterior as the disease progresses

  • Reduction in corneal sensitivity

• Complications: recurrent corneal erosions

• Treatment:

  • observation

  • Phototherapeutic keratectomy or lamellar keratoplasty

    • When VA significantly dec

Granular 2 Dystrophy (granular-lattice dystrophy or Avellino dystrophy)

• Combination of granular 1 and lattice dystrophy

• Symptoms: blurred vision, pain with RCE

• Presentation: discrete gray-white opacities made up of hyaline found in the anterior stroma combined with lines in posterior stroma

  • Deposits will be thorn-like, ring or stellate

  • Lattice lines develop latter but do not cross as they do in lattice

    • appear whiter & less refractile

• Treatment: observation, treatment of RCE

Macular dystrophy

• stromal dystrophy 

• autosomal recessive

• Common in Iceland and Saudi Arabia

• Onset: first decade

• Symptoms:

  • Blurred vision (significantly in 2nd-3rd decade)

  • pain w/ RCE

• Presentation: deposits made up of mucopolysaccharides

  • Ill defined gray-white deposits that start in the central cornea and will migrate to limbus

  • Located in the anterior and posterior stroma

  • Entire cornea will appear cloudy as corneal collage fibrils are re-arranged

    • Eventually the collagen fibers will be replaced by fibrotic tissue and the cornea will thin

  • Decrease corneal sensitivity

  • Corneal edema will develop late in the disease process due to endothelial dysfunction

• Complications: blurred vision, recurrent corneal erosions (uncommon)

• Treatment

  • tx for RCE

  • Penetrating keratoplasty: recurrence is common

Macular Dystrophy Treatment

• tx for RCE (uncommon)

• Penetrating keratoplasty: recurrence is common

Schnyder (crystalline) corneal dystrophy

• autosomal dominant

• Onset: first decade with diagnosis coming in the second to third decade

• Symptoms: glare and significant vision loss/change in 6th decade

• Presentation: deposits are made up of lipid

  • Ring like opacity or central comma-shaped crystals

    • Subepithelial crystalline deposits and elevated blood lipid levels are seen in 50% of pts

  • Central corneal haze

  • Prominent arcus senilis (gradually moves central and causes haze)

  • Reduced corneal sensitivity

• Treatment: phototherapeutic keratectomy and penetrating keratoplasty

Schnyder (crystalline) corneal dystrophy Treatment

phototherapeutic keratectomy and penetrating keratoplasty

Fuch’s corneal dystrophy

• endothelial dystrophy

• Inheritance pattern: autosomal dominant

  • sporadic

• More common in females

• Onset: early onset presents in third decade

  • Late onset presents in sixth decade

• Symptoms:

  • Blurred vision that is worse in the morning

  • Photosensitivity

  • Pain can develop with disease progression

• Presentation: characterized by endothelial cell loss

  • Stage 1: corneal guttata = thickening Descemet membrane that appears dark on specular reflection

    • starts central & spreads to periphery

    • usually asymptomatic

  • Stage 2: corneal guttata and corneal edema

    • guttata begin to coalesce

    • Endothelial cells start to change shape and enlarge

    • Corneal edema begins as endothelial cell count starts to decrease

    • edema = blurry vision that improves throughout day

  • Stage 3: bullous keratopathy

    • edema causes epithelium to detach from basement membrane

      • Blister like lesion or bullae develop

      • Blisters can rupture leading to extreme pain

      • risk of corneal infection

    • Epithelial microcyst will be present

  • Stage 4: Corneal scarring and vascularization

    • Subepithelial fibrous tissue deposition

      • from chronic corneal edema

      • significant reduction in VA

      • minimal pain

Fuch’s corneal dystrophy Treatment

• Stage 1 = observation

• Stage 2 = hypertonic salt solution

• Stage 3 = bandage contact lens for ruptured bullae

  • Topical antibiotic if concerned about secondary infection

  • DSAEK: Descemet membrane-stripping endothelial keratoplasty

  • DMEK: Descemet membrane endothelial keratoplasty

• Stage 4 = PK: penetrating keratoplasty

Posterior polymorphous dystrophy (PPMD)

• endothelial

• Inheritance pattern: autosomal dominant

• Onset: first decade

• Pathophysiology: abnormal endothelial cell proliferation

  • The abnormal proliferation causes an abnormal basement membrane to develop and thickening of Descemet membrane

  • Endothelial cells become more epithelial in nature-develop microvilli

• Symptoms:

  • Asymptomatic

  • Blurred vision when corneal edema develops

• Presentation:

  • Geographic gray opacities: least common finding

    • at lvl of Descemet

    • stromal haze adjacent

    • May have whirl like pattern

  • Vesicular lesions: pathognomonic for PPMD

    • Appears as circular or oval transparent cysts with gray halo-gives a blister appearance

    • in a line or clusters

  • Horizontal bands in inferior cornea

    • Range from 2-10mm in length

    • Will have a parallel scalloped or flaky edge

• Complications: secondary glaucoma or iris abnormalities (migration of endothelial cells causes angle closure)

• Treatment:

  • Observation

  • Treatment of corneal edema similar to Fuch’s

  • Treatment of complications

Posterior polymorphous dystrophy (PPMD) Treatment

• Observation

• Treatment of corneal edema similar to Fuch’s

• Treatment of complications

Corneal degeneration

• slow and steady deterioration of corneal tissue

• occurs in the periphery

• Will affect several layers of the cornea

• Unilateral and asymmetric

• Occurs in older patients

• No genetic component

Corneal degenerations share which of the following characteristics with corneal dystrophies?

Both are non-inflammatory

Punctate epithelial erosions

• tiny epithelial defects

  • stain with fluorescein or Lissamine Green/Rose Bengal

• Early sign of corneal compromise

• Can be located throughout the cornea (area helps determine cause)

Superior PEEs=

vernal keratoconjunctivitis, SLK, floppy eyelid

Interpalpebral PEEs=

dry eye

Inferior PEEs=

chronic blepharitis

Diffuse PEEs=

viral infection

Central PEEs=

contact lens related

Punctate epithelial keratitis (PEK)

• swollen epithelial cells

• Presentation: granular, opalescent swollen epithelial cells

• stains with Lissamine Green/Rose Bengal; variable with fluorescein 

  • punctate staining will be seen

• Seen with: viral infections, Thygeson superficial punctate keratitis

Subepithelial infiltrates

• non-staining inflammatory cells

  • unclear margins

• Located below epithelium

• Inflammatory cells are released from limbal vasculature

• Seen with: adenoviral keratoconjunctivitis, HZO, marginal keratitis

Filaments

• Mucus strands attached to the cornea

  • Will attach where there is an epithelium break

  • Tear debris will surround mucus strand

• Commonly seen with dry eye, SLK

Superficial punctate keratitis

• non-specific round corneal epithelial disruption of round morphology

• commonly seen w/ corneal disease

• has inflammation with it

  • only difference from PEEs

Epithelial edema

• swelling of cornea

• Will present as small epithelial vesicles

• seen w/ endothelial compromise

Corneal Neovascularization

• blood vessel growth onto cornea at limbus

• Sign of chronic ocular irritation or hypoxia

Pannus

superficial neovascularization with subepithelial degeneration

Deep Infiltrates of cornea

• inflammatory cells, cellular debris, and tissue necrosis located in the anterior stroma

• appear white to grey

• conj. hyperemia will also be present

Corneal Ulceration

• excavation of corneal tissue w/ epithelial defect

• seen with deep infiltrate

Melting of cornea

• Tissue disintegration

• in severe corneal disease

• Corneal infiltrate may or may not be seen

Folds in Descemet

• dark, deep-appearing, criss-cross lines in posterior stroma

• cornea can appear hazy d/t corneal edema

• commonly seen after surgery

Breaks in Descemet

from corneal enlargement (infantile glaucoma), birth trauma (forceps), or keratoconus

Descemetocele

• protrusion of Descemet membrane into the anterior layers of the cornea

• seen w/ severe ulceration

Corneal dystrophies

• group of slowly progressive, usually bilateral corneal opacification that may cause decreased vision and discomfort

• typically only affect one layer of cornea

  • Starts out in the center of the cornea and migrate to the periphery

• Non-inflammatory

• Genetic with majority being autosomal dominant

• Occurs in younger patients

Epithelial Basement Membrane Dystrophy (Cogan or Map-Dot-Fingerprint)

• most common; affects 40% of population

  • in 70% of individuals over 50

• Onset: 2nd decade

• More common in females

• Inheritance pattern: no clear inheritance pattern

  • Can be due to trauma and some consider condition more of a degeneration

• Pathophysiology: synthesis of an abnormal basement membrane

  • Faulty adhesion between the basement membrane and epithelium

  • BM extends into epithelium & causes it to heap up

    • elevated tissue = map

    • Migrated cellular material becomes trapped and develops dots and other cystic changes

    • Adjacent rows of thickened and elevated epithelium will develop into fingerprints

• Symptoms: asymptomatic

  • if progressed: blurry vision worse in AM, diplopia, dry eye, foreign body sensation

• Presentation: maps, dots or fingerprints

  • Maps: appear as large geographic lesions

  • Dots: commonly seen with maps

  • Fingerprints: appear as line

    • commonly seen in isolation

  • Due to elevated epithelium, lesions will appear to have negative staining

• Complications: recurrent corneal erosions (RCE) in inferior third

  • Due to the hemidesmosomes inability to anchor the epithelium to the anterior stroma

  • occurs in 3rd decade

  • Symptoms of RCE: severe pain, usually upon waking

  • Presentation: epithelial defect-stains with fluorescein

• Treatment: depends on the symptoms

  • none if asymptomatic

  • artificial tears for blurry vision, dry eye, FBS

  • for mild/RCE prevention:

    • Hypertonic salt solution (helps keep the epithelium anchored to the stroma)

    • Topical steroids

    • Oral tetracycline/doxycycline

EBMD Treatment

• Asymptomatic: none

• Blurred vision, foreign body sensation and dry eye symptoms: artificial tears

• For mild cases/RCE prevention:

  • hypertonic salt solution (keeps anchored)

  • topical steroids

  • oral tetracycling/doxycycline

• For moderate to severe cases/history of RCE:

  • Debridement: surgical intervention to remove irregular epithelium on active RCE

  • Phototherapeutic keratectomy-done with excimer laser

  • Stromal puncture: causes scar tissue which will anchor the epithelium to stroma

  • Bandage contact lens

Arcus senilis

• most common peripheral corneal opacity

• Symptoms: None

• Onset: all ages

  • Younger individuals: related to systemic disease (high lipids)

  • Older individual: no systemic association

• Presentation: stromal lipid deposition

  • Starts superior and inferior and progressed circumferentially

  • Will be 1mm wide

  • Will have a clear zone between corneal opacity and limbus

• Treatment: none unless suspect systemic association

Vogt limbal girdle

• common peripheral corneal opacity

• Onset: elderly individuals

  • Found in 60% of individuals over the age of 40

• Symptoms: asymptomatic

• Presentation: whitish crescentric limbal bands made up of chalk like flecks

  • Occurs at 9 and/or 3 o’clock

  • More common nasal, can go temporal

  • May present with holes within the lesion; gives “swiss cheese” appearance

• Treatment: none

Crocodile shagreen

• Onset: elderly individuals

• Symptoms: none

• Presentation: greyish-white, polygonal stromal opacities that resemble crocodile skin

  • Opacities are ill defined (hazy) and separated by clear spaces

  • in anterior stroma

• Treatment: none

Band keratopathy

• Symptoms: asymptomatic until advanced disease occurs and then the patient presents w/ irritation (once migrated over visual axis)

• Causes:

  • Ocular: anterior uveitis, glaucoma, phthisis bulbi, chronic corneal edema and keratitis

  • Age: common in elderly

  • Metabolic: hyperparathyroidism, vitamin D toxicity, sarcoidosis, end stage renal failure

• Presentation: calcium salts in Bowman layer, epithelial basement membrane and anterior stroma; starts nasal & temporal

  • Clear zone between deposits and limbus

  • Will have transparent holes within deposits

  • Gradual extension to central cornea

  • Advanced lesions become nodular and elevated = neg stain

• Treatment: chelation

  • Removal of the epithelium and calcium then EDTA is applied until calcium is removed

Band keratopathy Treatment

Chelation: Removal of the epithelium and calcium then EDTA is applied until calcium is removed

• chemical will cause abrasion

Spheroidal degeneration

• common in males

• Cause: UV light; more common in those who spend hours outdoors

• Symptoms:

  • asymptomatic

  • Blurred vision in individuals with advanced cases

• Presentation: amber colored granules in anterior stroma

  • Granules replace Descemet membrane

  • In advanced disease corneal opacification and central spread will occur

  • Lesions will also protrude above the corneal surface

    • foreign body sensation

• Treatment:

  • UV protection

  • Superficial lesions: phototherapeutic keratectomy

  • Advanced disease: Lamellar keratoplasty or penetrating keratoplasty

Spheroidal degeneration Treatment

• UV protection

• Superficial lesions: phototherapeutic keratectomy

• Advanced disease: Lamellar keratoplasty or penetrating keratoplasty

Salzmann nodular degeneration

• Average age of onset: 59 years old

• Female>Male

• Cause: chronic corneal irritation or inflammation

  • Trachoma, chronic blepharitis, chronic allergic keratoconjunctivitis, dry eye

• Symptoms: dryness, foreign body sensation, decreased vision

• Presentation: superficial stromal opacities that progress to elevated whitish to blue-grey nodular lesions

  • nodules are round or elongated

  • Nodules of hyaline tissue and are located anterior to Bowman layer

• Treatment:

  • lubrication

  • Surgery: superficial keratectomy, phototherapeutic keratectomy or lamellar keratoplasty

    • smooths surface

Salzmann nodular degeneration Treatment

• lubrication (dry)

• Surgery: superficial keratectomy, phototherapeutic keratectomy or lamellar keratoplasty

  • smooths surface of cornea

Corneal ectasias

• non-inflammatory (white eye)

• progressive

• always bilateral but asymmetric

• Characterized by corneal thinning and bulging of the cornea

Keratoconus

• Inheritance pattern: autosomal dominant

• Onset: teens to twenties

• Systemic association: Down Syndrome, Ehlers-Danlos, Marfan syndrome and Osteogenesis imperfecta

• Ocular association: vernal keratoconjunctivitis and eye rubbing

• Symptoms: blurred vision with multiple spectacle changes

  • Pain will be reported with complications

• Presentation:

  • Refractive findings: high amounts of myopia and irregular astigmatism (see scissoring)

  • Steep Keratometry readings

    • Mild: <48 D

    • Moderate: 48-54 D

    • Severe: >54D

  • Slit lamp findings:

    • Conical corneal protrusion inferior

    • Stromal thinning inferior and scarring

    • Fleischer ring = iron deposit at base of cone

    • Vogt’s striae = vertical lines in Descemet

    • Munson sign = lid V shape in downgaze

    • Charleaux sign = Oil droplet when viewing red reflex

  • Corneal topography: inferior steepening and distortion of Placido’s disc

• Complications:

  • Hydrops: breaks in Descemet membrane causing aqueous into the stroma resulting in stromal edema

    • Pain, photophobia, epiphora, dec vision

    • Corneal haze, conj. hyperemia, ant chamber rxn

• Treatment:

  • Spectacles: best corrected visual acuity is reduced in keratoconic patients

  • Rigid contact lens: creates a spherical and regular refractive surface over an irregular cornea

  • Scleral lenses: large contact lens that rest on sclera

  • Intacts: half circle pieces of polmethylmethacrylate (PMMA) inserted into mid-stroma to flatten cornea

  • Corneal cross linking: UVA strengthens cornea via oxidation

  • Penetrating keratoplasty (PK)

Hydrops

• breaks in Descemet membrane causing aqueous into the stroma resulting in stromal edema

• complication of keratoconus

  • Occurs in approximately 3% of keratoconic patients

  • Seen in advanced keratoconus

• Symptoms: pain, photophobia, epiphora and decreased vision

• Presentation: corneal haze

  • Conjunctival hyperemia, anterior chamber reaction

• Treatment (heal in 6-10wks):

  • Topical cycloplegics (helps with pain control)

  • Hypertonic salt ointment

  • Topical antibiotic solutions (helps prevent secondary infection)

  • Topical NSAID

  • Topical corticosteroid

  • Bandage contact lens

Keratoconus Treatment

• Spectacles: best corrected visual acuity is reduced in keratoconic patients

• Rigid contact lens: creates a spherical and regular refractive surface over an irregular cornea

• Scleral lenses: large contact lens that rest on sclera

  • vault cornea to create regular refractive surface

• Intacts: half circle pieces of polmethylmethacrylate (PMMA) inserted into mid-stroma

  • flattens cornea

  • requires clear visual axis

  • removable

• Corneal cross linking

  • halts progression

  • Riboflavin with UVA exposure will strengthen the cornea

    • Cornea is strengthen by increasing covalent bonds by oxidation

    • stability improves

  • can be done by removing corneal epithelium (better results) or keeping it

• Penetrating keratoplasty (PK)

  • Removal of the entire diseased/scarred cornea and replaced with a donor cornea

  • Complications: PEEs, GPC, wound leak, shallow ant. chamber, iris prolapse, uveitis, inc. IOP, Khodadoust line from rejection

What do rigid contact lens allow for?

regular refractive surface

Pellucid marginal degeneration

• Onset: adulthood

• Symptoms: blurred vision

• Presentation:

  • Refractive error findings: ATR astigmatism

  • Slit lamp findings: crescentric 1-2mm band of corneal thinning located inferior

    • between 4 and 8 o’clock

    • Will be 1mm away from the limbus

    • Fleischer ring, Vogt’s striae and hydrops are rare

  • Corneal topography: band of inferior steepening

    • runs from 4 to 8 o’clock

    • kissing bird or butterfly topography

• Treatment

  • spectacles

  • contact lenses: toric soft contact lenses, gas permeable contact lenses, scleral contact lenses

  • Lamellar keratoplasty

Pellucid marginal degeneration Treatment

• spectacles

• contact lenses: toric soft contact lenses, gas permeable contact lenses, scleral contact lenses

• Lamellar keratoplasty

Keratoglobus

• Onset: birth or adulthood

  • Presentation at birth is associated with Ehler-Danlos, Leber congenital amaurosis & blue sclera

  • Presentation in adulthood is thought to evolve from keratoconus or pellucid marginal degeneration

• Symptoms: decreased visual acuity

• Presentation:

  • Refractive error findings: myopia and irregular astigmatism

  • Slit lamp findings: globular cornea with generalized corneal thinning

    • hydrops are rare

    • corneal diameter is normal

  • Corneal topography: steepening limbus to limbus

• Complications: corneal rupture with relatively mild trauma

• Treatment:

  • spectacles

  • scleral contact lenses

  • lamellar keratoplasty

Wilson disease (hepatolenticular degeneration)

• Onset: teenage years to early twenties

• Cause: deficiency in a copper carrying blood protein that results in excess deposition of copper in tissues especially the liver, brain, and eyes

• Systemic presentation: liver disease, neurological symptoms, psychiatric disturbance & death if left untreated

  • Liver disease: will see yellowing of the skin and sclera, swelling of legs and abdomen, bruising, and prolonged bleeding & excessive tiredness

  • Neurological symptoms: tremor, involuntary movements, difficulty swallowing & speaking, muscle rigidity

  • Psychiatric symptoms: depression, schizophrenia, personality changes

• Presentation:

  • Brownish-yellow ring of copper (Kayser-Fleischer ring) in Descemets

  • May have an associated sunflower cataract

• Treatment:

  • Systemic treatment to lower copper levels

  • No ocular treatments required

Fabry disease

• Inheritance pattern: X-linked

  • males>females

• Cause abnormal tissue accumulation of glycolipid

• Systemic manifestations: cardiomyopathy and renal disease

• Presentation:

  • White to golden-brown corneal opacities in a vortex pattern

  • Other ocular signs: wedge or spoke shaped posterior cataract, conjunctival vascular tortuosity and aneurysms, retinal vascular tortuosity

• Treatment:

  • Treatment of systemic condition

  • No ocular treatment

Interstitial Keratitis

• inflammation of the corneal stroma without primary involvement of the epithelium or endothelium

  • Inflammation is thought to be an immune mediated response triggered by an antigen

• Causes: syphilis, herpes simplex, varicella zoster

Syphilitic Interstitial Keratitis

• Primarily seen with congenital syphilis infection but can occur with acquired syphilis infection

• Caused by Treponema pallidum

• 4 Stages:

  • Primary: sores at the site of the infection

  • Secondary: skin rash, swollen lymph nodes and fever

  • Latent: no signs or symptoms

  • Tertiary: affects organ systems (heart, brain)

• Onset: between the ages of 5 to 25

• Bilateral in 80% of cases

• Symptoms: blurred vision

• Presentation:

  • Acute: 

    • Deep stromal blood vessels and corneal edema (salmon patch)

    • Anterior uveitis with keratic precipitates

    • Conjunctival injection

  • Chronic:

    • Deep corneal haze or scarring

    • Ghost vessels (deep blood vessels that contain little to no blood)

    • stromal thinning (can cause perforation)

    • If recurrence occurs the ghost vessels may fill with blood and may bleed into the cornea

• Complications:

  • deep stromal scarring with thinning

  • Astigmatism

  • Band Keratopathy

• Treatment:

  • Lab work up for detecting syphilis

  • Referral for systemic control of the infection

  • Topical steroid

  • Topical cycloplegia

Syphilitic Interstitial Keratitis Treatment

• Lab work up for detecting syphilis

  • FTA-ABS: will determine if the individual has syphilis

  • RPR or VDRL: will determine if the infection is active or not

• Referral for systemic control of the infection

• Topical steroid

  • it’s inflammatory!

• Topical cycloplegia

  • rests ciliary body = pain control

Congenital Syphilis

• infection crosses placenta & infects the fetus

• Systemic signs:

  • Early signs: failure to thrive, maculopapular rash, mucosal ulcers

  • Late signs: sensorineural hearing loss, saddle-shaped nasal deformities, jaw abnormalities - underdeveloped maxillary bone and prominent mandibular bone, teeth abnormalities, joint abnormalities

  • Ocular signs: anterior uveitis, interstitial keratitis, dislocated/subluxated lens, cataract, optic atrophy, salt and pepper pigmentary retinopathy, Argyll Robertson pupil

HSV 1

affects face, lips, eyes

HSV 2

• sexually transmitted

  • Can be transferred from mother to infant during birth

• Resides in neuronal ganglion

  • trigeminal for the eye

Herpes Simplex Keratitis

• Most common infectious cause of blindness in developed countries

• Primary infection: typically occurs in childhood

  • spread by droplets or direct inoculation

  • Uncommon during the first six months of life due to maternal antibodies

  • Present as mild fever, malaise and upper respiratory tract symptoms; can have bleph or follicular reaction after age 2

• Recurrent infection:

  • Triggers: fever, hormonal change, UV radiation, trauma

  • Risk factors for severe disease: topical steroid use, atopic eye disease, immunodeficiency or suppression, malnutrition

  • Corneal scarring will be seen with every recurrence

    • VA loss

Epithelial Keratitis from Herpes Simplex

• Associated with active virus replication**

• Symptoms: mild to moderate discomfort, hyperemia, photophobia, tearing and blurred vision; lack of pain

• Presentations (in chronological order):

  • reduced visual acuity

  • Swollen opaque epithelial cells, will present in a punctate or stellate configuration

  • Dendritic ulceration-linear branching

    • Frequently located centrally

    • Ends of the dendrite (terminal bulbs) will stain with Rose Bengal

  • Reduction of corneal sensation

  • Mild subepithelial haze (may take weeks to heal)

  • Mild anterior chamber reaction

  • Follicular conjunctival reaction

  • lid vesicles (can be seen at ulceration)

  • elevated IOP

    • Trabecular meshwork’s inflamed

• Complications from steroids:

  • Geographic ulcer

• Treatment:

  • Topical antiviral solution or gel

  • Topical cycloplegia (for pain of AC rxn)

  • Debridement for resistant cases

  • Oral antiviral medications (for when topical isn’t tolerated)

  • Topical glaucoma medications if IOP is elevated (avoid prostaglandins)

Epithelial Keratitis Treatment

• Topical antiviral solution or gel

• Topical cycloplegia (for pain of mild ant. chamber rxn)

• Debridement for resistant cases

  • epithelium is removed 2mm from the edge of the ulcer

• Oral antiviral medications (for when topical isn’t tolerated)

  • good for long term, recurrence (PCP needs to maintain their health)

• Topical glaucoma medications if IOP is elevated (avoid prostaglandins)

What meds do you never use for treating IOP on a patient with a Herpes reaction/infection?

prostaglandins

Stromal Keratitis from Herpes Simplex

• Cause: immune mediated response to viral antigens**

  • Severe cases may be a reaction to live virus in the stroma

• 2 Types:

  • Immune stromal keratitis

  • Necrotizing interstitial keratitis

• Treatment:

  • Topical steroid (immune rxn, not active infection!)

  • Topical antiviral-if epithelial defect is present

  • Oral antiviral

  • Penetrating keratoplasty if corneal perforation occurs

Immune Stromal Keratitis

• Symptoms: blurred vision, photophobia, glare and halos

• Presentation:

  • Stromal infiltrates with intact epithelium (neg stain)

    • Infiltrates can be focal, multifocal or diffuse

  • Stromal edema

  • Mild anterior uveitis

  • Chronic cases can cause stromal vascularization and corneal scarring

    • Lipid deposition may also be seen

Necrotizing Stromal Keratitis

• Presentation:

  • Dense stromal infiltration

    • Epithelial defect may or may not be present

  • Progressive necrosis with corneal perforation

  • Anterior uveitis with hypopyon

  • Increase IOP due to trabeculitis

Stromal Keratitis Treatment

• Topical steroid (immune rxn, not active infection!)

• Topical antiviral-if epithelial defect is present

• Oral antiviral

  • if recurrent & topical not doable

• Penetrating keratoplasty if corneal perforation occurs

Endothelial (Disciform) Keratitis

• Cause: immune response to viral antigen

• Symptoms:

  • Gradual onset of blurred vision with associated glare around lights

  • Discomfort-less than with epithelial disease

  • Hyperemia-less than with epithelial disease

• Presentation:

  • Disc-shaped stromal edema located in the center of the cornea

  • Epithelium will be intact

  • Mild anterior uveitis

  • Granulomatous keratic precipitates

  • Immune ring of stromal haze (Wessely ring)-signifies deposition of viral antigen and host antibody complexes

  • Increased IOP d/t trabeculitis

• Treatment:

  • Topical corticosteroid

  • Topical antiviral

  • Topical cycloplegic (provide comfort due to AC reaction)

Endothelial (Disciform) Keratitis Treatment

• Topical corticosteroid

• Topical antiviral

• Topical cycloplegic (provide comfort due to AC reaction)

Neurotrophic keratopathy

• complication of Herpes infection of cornea

• Cause: failure of corneal re-epithelization due to corneal anesthesia

  • Exacerbated by drug toxicity and reduction in tear production

• Presentation:

  • Sterile infiltrate with overlaying epithelial defect

  • Borders will be smooth

  • Stroma under the defect is grey and opaque

    • stromal will thin

  • central, interpalpebral

• Complications:

  • Secondary bacterial infection

  • Corneal thinning with perforation

  • Scarring

  • Neovascularization

• Treatment:

  • Discontinue medication if related to drug toxicity

  • Preservative free artificial tears

  • Cenegermin-bkbj ophthalmic solution (Oxervate)

  • Bandage contact lens

  • Amniotic membrane

  • Tarsorraphy

  • Preservative free topical antibiotic for secondary infection

Neurotrophic keratopathy Treatment

• Discontinue medication if related to drug toxicity

• Preservative free artificial tears

• Cenegermin-bkbj ophthalmic solution (Oxervate)

  • promotes neuron growth

• Bandage contact lens

• Amniotic membrane

  • put bandage CLs on after

• Tarsorraphy

• Preservative free topical antibiotic for secondary infection

HEDS I

• Herpes Stromal Keratitis: topical steroids and topical anti-viral provided a faster resolution when compared to topical anti-viral alone

• Time frame for the initiation of topical steroids is not crucial

• Adding oral anti-viral to topical anti-viral and topical corticosteroid is not beneficial

HEDS II

• Herpes Simplex Keratitis: adding oral anti-viral to topical anti-viral does not prevent the patient from developing stromal disease

• Oral anti-viral reduces the recurrence of herpetic eye disease

Herpes Zoster Ophthalmicus

• Cause: Varicella-Zoster virus

• Onset: sixth to seventh decade

  • Can be seen in younger individuals

  • Symptoms tend to be worse in older individuals compared to younger individuals

• Common in immunocompromised individuals

• Resides in cranial nerve ganglia until re-activated

• Acute Presentations:

  • epithelial keratitis (2 days after); psuedodendrites

  • nummular keratitis (10days after)

  • stromal/interstitial keratitis (3wks after)

  • disciform keratitis

  • Conjunctivitis: follicular and/or papillary reaction

  • Episcleritis (occurs at the onset of the rash)

• Chronic Presentations:

  • Neurotrophic keratopathy

  • Mucus plaque keratitis

Acute Shingles

• Prodromal phase: occurs 3 to 5 days prior to the appearance of the rash

  • Will consist of tiredness, fever, malaise and headache

  • Affected dermatome will experience superficial itching, tingling or burning sensation

    • Additional symptoms include severe boring or lancing pain that is constant or intermittent

• Presentation: painful erythematous areas with a maculopapular rash

  • Rash will respect the midline

  • Vesicles will appear within 24 hours

    • Vesicles will be in grouped together and will coalesce within 2-4 days

    • Will crust and completely resolve in 2-3 weeks

  • Eyelid edema of the upper and lower lid

  • Multiple dermatomes may be involved with immunocompromised patients

• Treatment:

  • Oral antiviral: given within 72 hours of the onset of the rash

    • Will reduce the severity and duration of the acute episode and risk for post herpetic neuralgia

    • If a patient presents after 72 hours but still has vesicles, consider prescribing oral antiviral

  • Topical antibiotic ointment for vesicles

Acute Shingles Treatment

• Oral antiviral: given within 72 hours of the onset of the rash

  • Will reduce the severity and duration of the acute episode and risk for post herpetic neuralgia

  • If a patient presents after 72 hours but still has vesicles, consider prescribing oral antiviral

• Topical antibiotic ointment for vesicles

  • prevent secondary infection

Epithelial keratitis from Herpes Zoster Ophthalmicus

• develops in 50% of patients 2 days after onset of the rash

• Will spontaneously resolve in a few days

• Characterized by pseudo-dendrites similar to herpes simplex dendrites

  • Will have taper ends rather than terminal bulbs

  • Will stain better with Rose Bengal than fluorescein

Nummular Keratitis from Herpes Zoster Ophthalmicus

• develops at the site of the epithelial lesions

• Occurs 10 days after the onset of the rash

  • after psuedodendrite stage

• Characterized by fine granular subepithelial deposits

  • Deposits will have a halo of stroma haze surrounding it

Stromal (interstitial) Keratitis from Herpes Zoster Ophthalmicus

• occurs 3 weeks after the onset of the rash

• Significant scarring can occur

  • dec VA

Disciform keratitis (immune mediated endothliitis) from Herpes Zoster

• Less common than with HSV

• Corneal decompensation may occur

Neurotrophic keratopathy from Herpes Zoster Ophthalmicus

• from chronic zoster

• Occurs in 50% of patients

• Tends to be mild and will resolve over several months

• similar to HSV infections

Mucus plaque keratitis from Herpes Zoster Ophthalmicus

• chronic

• occurs between 3-6 months of onset of symptoms

• Elevated mucus plaques that stain with Rose Bengal

• If left untreated, plaques will become scars

Acute Treatment of Herpes Zoster Ophthalmicus

• Epithelial keratitis: preservative free artificial tears

  • no active infection = no antibiotic

• Nummular keratitis/stromal keratitis/disciform keratitis: topical corticosteroid

  • Require slow taper to prevent recurrence for nummular and stromal keratitis

Chronic Treatment of Herpes Zoster Ophthalmicus

• Neurotrophic keratopathy: same treatment as neurotrophic keratitis in Herpes Simplex

• Mucus plaque keratitis: debridement, then topical steroid

Post-herpetic neuralgia

• pain that persist for more than one month after the resolution of the rash

• Develops in 75% of individual over the age of 70

• Presentation: intermittent or constant pain

  • Pain may be worse at night and aggravated by touch or heat

• Treatment: cold compresses

  • Topical capsaicin cream, tricyclic antidepressants, anticonvulsant medications