Cornea Flashcards
What structure of the eye has the highest refractive power?
The cornea (45D)
Function of the cornea
Focusing light and also filters out UV rays.
Lengths of the cornea
10.6mm vertical length and 11.7mm horizontal length
8.7.8mm anterior curvature and 6.5mm posterior curvature
Thickness of the cornea
Thickness = 555um in the centre, thicker at the periphery
What is the stroma of the cornea composed of
Dermatan sulphate and keratan sulphate are found in the stroma
The cornea is described as an immune-privileged structure
lacks MHC II cells
Cornea innervation
CNV1 via long ciliary nerves
Layers of the cornea (superficial to deep)
- Epithelium: stratified non-keratinised squamous epithelium
- Bowman’s layer
- Stroma: thickest layer, and contains collagen type 1
- Descemet’s membrane: contains collagen type 4
- Endothelium: maintains corneal transparency by mitochondrial pumping of water from stroma to aqueous
What are Palisades of Vogt
radial folds of the cornea at the superior and inferior limbus (the boundary between the cornea and sclera)
What endothelial cell density is considered corneal endothelial failure
Endothelial cell density < 800mm²
What cell density is required for endothelial donors
> 1500mm² density
Specular microscopy
- Used to study the corneal endothelium at high resolution
- Corneal endothelial cells are hexagonal and the normal adult has a cell density of around 3000 cells/mm2
- The number of corneal endothelial cells decrease with age
- Highest endothelial cell density is at the periphery
normal range for corneal endothelial cell density
1500-3500 cells/mm²
Corneal Topography
Produces an image of the shape of the corneal surface
Principally used in the evaluation of corneal ectasias and astigmatism
Oculus Pentacam report of corneal thickness and surface shape
What 2 investigations can be used to measure corneal thickness
Pachymetry and OCT
Fluorescein Staining
Used in the identification of corneal epithelial lesions
Corneal epithelial defects stain green with fluorescein.
Fluorescein staining on a patient with corneal abrasion. The arrow indicates a stained section of the cornea where epithelial defects are likely to be found.
Management of Epithelial defects
May require re-epithelialization to promote healing
Lubrication with artificial tears
Bandage contact lenses
PO doxycycline
Persistent unresponsive epithelial defects:
* Amniotic membrane graft
* Autologous serum drops
Doxycycline in management of epithelial defects
Doxycycline is a matrix metalloproteinase (MMP) inhibitor which promotes wound healing
Management of Exposure/neurotrophic keratopathy
Management involves closing the lids through:
* Taping of the lids
* Botox to the levator muscle
* Gold weight upper lid insertion for facial nerve palsy
* Tarsorrhaphy
Smoking and epithelial healing
Smoking hinders epithelial healing and should be stopped
Management of Limbal stem cell deficiency
Limbal stem cell transplantation
The Palisades of Vogt can be lost in cases of limbal stem-cell failure
Management of Dry eye
Artificial tears and lubricants
Punctal plugs
Keratoplasty
Keratoplasty (corneal transplant), can be full-thickness (penetrating) or partial thickness (anterior or posterior lamellar).
A patient who has undergone penetrating keratoplasty.
Indications for keratoplasty
Optical - keratoconus (commonest), scarring, corneal dystrophies, bullous keratopathy
Therapeutic - removal of infected corneal tissue
Types of Keratoplasty
Difference between DSAEK and DMEK
The key difference between DSAEK and DMEK is that DSAEK adds stroma. Remember ‘S’ for Stroma.
In what two groups of people is Bacterial keratitis most commonly seen in?
contact lens wearers and in post-op patients
Pathogens in bacterial keratitis
Pseudomonas Aeruginosa - commonest cause of bacterial keratitis in contact lens wearers
Other causes include: Staphylococcus aureus and Streptococci
Presentation of bacterial keratitis
Keratitis typically presents with an acutely painful unilateral red eye with discharge
Pseudomonas infection is seen in prolonged contact lens wear
Investigation for bacterial keratitis
Corneal scraping for microbiology
Management of bacterial keratitis
Topical broad-spectrum antibiotics (e.g fluoroquinolones such as ofloxacin)
Subsequent specific antibiotics are guided by sensitivity testing
Compare presentation of fungal vs bacterial keratitis
Presenting symptoms are milder than bacterial infections. Look for immunocompromise or trauma associated with plants/soil in the history.
Candida
Patients with AIDS/ immunocompromise/diabetes
Plaque corneal ulcer with expanding infiltrate
Aspergillus/Fusarium
History of trauma associated with contact of plants or soil
White, feathery corneal lesions
Management of Fungal Keratitis
Corneal scraping for microbiology
Candida → Voriconazole or amphotericin B drops
Filamentous (aspergillus/fusarium) → Natamycin drops
Severe infection → add Chlorhexidine
What may provide a faster diagnosis than culture
(for fungal keratitis)
Confocal microscopy can provide a faster diagnosis than culture
Acanthamoeba keratitis
A protozoan disease that can be clinically severe and is notoriously difficult to treat.
Pathology of Acanthamoeba keratitis
Caused by the protozoan: Acanthamoeba
Lives in soil, fresh water and the upper respiratory tract.
Presentation of Acanthamoeba keratitis
Initial presentation is similar in bacterial keratitis
Neural ring-shaped corneal infiltrates are specific and develop over time
Investigation for Acanthamoeba keratitis
Culture medium is non-nutrient agar with E.coli
Confocal microscopy shows amoebic cysts
Infection is associated with exposure to freshwater or soil, especially in contact lens wearers
Management of Acanthamoeba keratitis
Topical polyhexamethylene biguanide (PHMB) or chlorhexidine
(Acanthamoeba Keratitis is widely considered to be an orphan disease. Drug companies haven’t adapted treatments because of the rarity of the disease)
Marginal Keratitis
An autoimmune reaction against Staphylococcal toxin, which characteristically affects the peripheral cornea.
Pathology of Marginal Keratitis
- A type 3 autoimmune inflammation of the peripheral cornea.
- Triggered by hypersensitivity to Staphylococcal toxin (most commonly Staph Epidermidis)
- Inflammation occurs at the superior and inferior limbus where the lid contacts the cornea.
- More common in patients with staph associated infections such as blepharitis and acne rosacea
Management of Marginal Keratitis
Steroid drops
Lid hygiene for blepharitis
What are the 2 important forms of Herpes keratitis?
Simplex and Zoster
Most common infectious cause of corneal blindness in developed countries
Herpes simplex keratitis
How can Herpes simplex keratitis be furthur classified
According to the layer of the cornea that is affected: epithelial or endothelial.
Pathology of Herpes simplex keratitis
Primary herpes simplex infection causes blepharoconjunctivitis and the virus remains dormant within the trigeminal nerve ganglion. Subsequent reactivation of the virus lead to recurrent epithelial keratitis (secondary herpes simplex infection).
Herpes simplex endothelial (also known as disciform) keratitis is an autoimmune hypersensitivity reaction to the herpes simplex antigen and manifests differently to epithelial keratitis.
Dendritic corneal ulcer seen in herpes epithelial keratitis.
Investigations for HSK
Simplex keratitis is a clinical diagnosis but swabs can be taken for PCR/Giemsa stain.
Giemsa stain would show multinucleated giant cells
Compare Epithelial vs Endothelial (Disciform) HSK
What is a Wessely ring
Wessely ring is not specific to HSV keratitis, it is the circular deposition of an antibody-antigen complex, visible in the cornea
Herpes Zoster Ophthalmicus
Herpes zoster ophthalmicus is essentially shingles of the eye. It can be severe and needs prompt treatment
Pathology of HZO
- Primary infection of Varicella-zoster leads to chickenpox.
- Secondary (re)infection leads to shingles (herpes zoster).
- Shingles of the eye (CNV1 dermatome) is herpes zoster ophthalmicus.
Presentation of HZO
- Dermatomal vesicular rash and neuropathic pain.
- Hutchinson sign: Rash on tip of nose indicates a high probability of ocular involvement because the tip of the nose is supplied by the nasociliary branch of CNV.
- Conjunctivitis and epithelial keratitis with non-ulcerative pseudodendrites that do not stain with fluorescein
Management of HZO
Acyclovir Oral 800mg 5 times per day
Interstitial Keratitis (IK)
Interstitial keratitis is an inflammation of the corneal stroma. There are many causes of IK
Pathology of IK
Inflammation of the corneal stroma in the absence of primary epithelial or endothelial involvement.
Over time, this inflammation leads to scarring which looks feather-like and has associated ghost vessels.
Causes of IK
Erythema migrans in patient with Lyme disease.
Peripheral Ulcerative Keratitis (PUK)
Inflammation around the corneal circumference rather than the central cornea is characteristic of some important corneal and extra-corneal diseases.
Pathology of PUK
- Inflammation/ulceration progresses centrally and posteriorly in most cases.
- PUK is typically either caused by infection or a systemic autoimmune disorder.
In practice, PUK is caused by infection until proven otherwise. Finding PUK in isolation, in the absence of other ocular pathology is suggestive of a systemic autoimmune disorder.
Systemic Autoimmune Associations with PUK
- Rheumatoid arthritis - the most common systemic autoimmune cause of PUK
- Granulomatosis with polyangiitis (GPA)
- Crohn’s
- SLE
- Polyarteritis nodosa
Filamentary keratitis
A common condition caused by mucous and strand adhesion to the corneal surface due to degenerations of the corneal epithelium. It can cause severe discomfort.
Presentation of Filamentary keratitis
Typically found in cases of abnormal tear film such as dry eye, LASIK and contact lens wearers.
Patients present with watery, irritated red-eye with a foreign body sensation.
Investigations for Filamentary keratitis
Rose bengal staining of the corneal surface shows comma-shaped lesions which move whilst blinking.
Slit Lamp biomicroscopy of filamentary keratitis
Management of Filamentary keratitis
Mucolytics such as acetylcysteine drops.
NSAID drops to address discomfort.
Mooren Ulcer
Mooren ulcer is a distinctive peripheral corneal disorder caused by autoimmune stromal ulceration.
Presentation of Mooren Ulcer
- Pain, photophobia and blurry vision.
- Characteristic peripheral corneal ulcer with an undefined edge
Management of Mooren Ulcer
- Immunomodulation with steroids.
- Oral tetracyclines can be used for their anti-collagenase effects.
What are corneal dystrophies?
A large group of disorders that involve the dysfunction of the corneal metabolic processes. This leads to an accumulation of various substances within the cornea, which ultimately obstruct vision. The disorders are typically characterised by anatomical location
List 2 Epithelial Dystrophies
Cogan (epithelial basement membrane)
Meesman (epithelial)
Cogan (epithelial basement membrane)
- The commonest corneal epithelial dystrophy
- Isolated cases with no family history
- Histology shows a thickened basement membrane over Bowman’s layer
- Retroillumination on slit-lamp shows: map-like subepithelial opacities, fingerprint-like subepithelial ridges and dot-like intraepithelial cysts
Meesman (epithelial)
- Non-progressive abnormality of epithelial metabolism
- AD inheritance, KR3/Kr12 mutation
- Histology shows cysts
- Treatment involves lubrication
Meesmann corneal dystrophy - Multiple opaque spots in the corneal epithelium
Reis-bucklers
Bowmans/Anterior Stromal
This is an anterior variant of granular stromal dystrophy (GCD 3) and is also known as CBD1
AD inheritance with TGFB1 gene defect
Histology shows replacement of Bowman’s by connective bands
Thiel-Behnke dystrophy
Also known as CBD2, is essentially a less severe CBD1. It is also AD inheritance with TGFB1 defect
Stromal Dystrophies
What is the most common corneal dystrophy overall?
Fuchs Endothelial Dystrophy
Pathology of Fuchs
Failure of sodium-potassium pump in corneal endothelium leads to fluid accumulation and endothelial cell loss
Corneal oedema can be exacerbated post eye surgery e.g post-cataract extraction.
Presentation of Fuchs
Typical presentation is an elderly woman with blurry vision worse in the morning, clearing towards the end of the day
Investigations for Fuchs
Slit-lamp examination can show a beaten metal appearance of the endothelium → represents the characteristic clinical sign of corneal guttata
The cornea will also be thicker when measured on pachymetry
Specular microscopy can show dark spots as evidence of endothelial cell loss.
Why are symptoms of Fuchs worse in the morning?
Symptoms are worse in the morning because the eyes are shut overnight and corneal fluid evaporation is limited.
The endothelial pump is dysfunctional so fluid accumulation occurs.
Throughout the day the eyes are open and blinking, this allows for better clearing of the accumulated fluid.
Management of Fuchs
- Topical sodium chloride drops and hairdryer application can help relieve symptoms
- Posterior lamellar keratoplasties (i.e DMEK & DSAEK) can be used to treat severe disease
What is an Ectasias
An ectasia is a distention/dilatation of a section of a structure beyond its normal physiological dimensions. The cornea is a curved structure and corneal ectasia refers to abnormalities in this shape.
Keratoconus
Abnormal outward protrusion and thinning of a section of the cornea.
Pathology of Keratoconus
Progressive stromal thinning and apical coning of the cornea - exact cause is unclear
Abnormal shape of a section of the cornea leads to irregular astigmatism.
Severe keratoconus can lead to tearing of Descemet’s membrane and acute hydrops.
There are many disease associations with keratoconus: Down syndrome, Marfan syndrome, retinitis pigmentosa and Leber congenital amaurosis.
What is Keratoglobus?
A globular ectasia as opposed to the conical ectasia in keratoconus. It tends to present more at birth and is associated with generalised corneal thinning.
Presentation of Keratoconus
Typically bilateral and presents in adolescents.
Munson sign - lower lid protrudes on downward gaze
Vogt striae - corneal stromal striations seen on slit lamp
Oil drop and scissor reflex on ophthalmoscopy
Investigation for Keratoconus
Steep keratometry readings
Corneal topography (such as pentacam) is used for diagnosis and monitoring.
Keratoconus with Munson sign
Corneal topography in keratoconus. Note the irregular astigmatism and asymmetrical corneal thickness
Management of Keratoconus (depends on severity)
Mild(<48D of astigmatism) → Spectacles with cylindrical lenses
Step up to rigid contact lenses and corneal collagen cross-linking (Riboflavin drops and ultraviolet)
Severe (>54D of astigmatism) → Keratoplasty
Why is LASIK contraindicated in keratoconus
Because corneal thinning in keratoconus is unpredictable and you are unlikely to achieve any useful change in corneal shape with LASIK in these patients.
What is corneal collagen cross linking
Corneal collagen cross-linking involves soaking the stroma in riboflavin(b2) followed by UV light exposure
Pellucid Marginal Degeneration
Progressive thinning of the peripheral cornea, often inferiorly and bilaterally. This is a very rare disorder. There are two key things to know:
- Presents in adulthood with painless progressive bilateral blurring of vision over time
- Corneal topography shows a characteristic butterfly pattern
Neurotrophic Keratopathy
This is corneal ulceration caused by denervation.
Neurotrophic Keratopathy Pathomechanism
Loss of trigeminal innervation to cornea → intracellular oedema, loss of goblet cells → dry eye → ulceration
Causes of Neurotrophic Keratopathy
Stroke
Diabetes
Herpes
Presentation of Neurotrophic Keratopathy
Reduced corneal sensation (painless)
Persistent epithelial defect with stromal oedema and melting
Management of Neurotrophic Keratopathy
Topical lubrication
Anti-collagenase agents such as tetracyclines
Cenegermin
Ocular surface protection as discussed in ‘dry eye’
What is Cenegermin?
A topical recombinant human nerve growth factor which has shown some benefit in studies
Exposure Keratopathy
If the cornea is exposed to the external environment for a prolonged period, it becomes dry and ulcerated.
The cornea is extremely sensitive, if you keep your eyes open now, the burning sensation is mostly from the cornea.
Pathomechanism of Exposure Keratopathy
Lagophthalmos (inability to close the lids) leads to drying of the ocular surface and eventual ulceration
Causes of Exposure Keratopathy
CN7 Palsy
Conjunctival cicatrix
Ectropion
Exophthalmos
Presentation of Exposure Keratopathy
Dry gritty eye
Foreign body sensation
Management of Exposure Keratopathy
Same as ‘dry eye management’
List 3 important Metabolic Keratopathies
Kayser-Fleischer ring
