COMMON CASES

Dr. Riyad Banayot

Cornea

What do you see ?

Fleischer's ring (arrowed) around the cone Vogt's striae

Enlarged corneal nerves Corneal scar from previous hydrops

Keratoconus Early cases:

Thinning of the corneal apex with striation of the stroma and descemet's membrane (Vogt's striaes).

There is Fleischer's ring surronding the cone (blue light on the slit-lamp can improve its visualization).

Corneal nerves are prominent. Advanced cases:

Corneal scars from previous hydrops. Other examination:

Examine the fellow eye which may show a different stage of progression or corneal graft

Munson's sign (distortion of the lower lid on down-gaze) Rizzuti's sign (conical reflection on the nasal cornea

when a penlight is shone from the temporal side). Associated features:

Down's syndrome, atopic eczema, connective tissue disorders (Marfan's syndrome)

What is an acute hydrops? Is it an indication for urgent corneal graft ?

Acute hydrops develops from a break in the descemet's membrane leading to the entry of aqueous into the stroma causing stromal edema. The condition is painful and the cornea appears opaque.

It is not an indication for urgent corneal graft because the edema tends to resolve over weeks and months when the endothelium cells enlarge and grow over the descemet's break.

Cycloplegic and topical steroid are often used because of the pain and photophobia. Sodium chloride 5% can be used to reduce the edema.

Histological feature of keratoconus ?

There is fragmentation of Bowman's layer Thinning of the stroma and overlying

epithelium. The descemet's membrane shows folds

and breaks. Diffuse scarring is often present in the

stroma.

Treatment of keratoconus ? The main problem is high astimgatism

which is irregular and often progressive. Glasses can initially correct the

astigmatism and when these become ineffective hard contact lens is used.

When the vision can not be corrected with the contact lens or when the cornea becomes too steep for the contact lens, corneal graft is indicated.

New Technologies? Cross linking! Kerra rings!

Corneal topographies with irregular astigmatismIs it Keratoconus or Pellucid marginal degeneration ?

keratoconusThe topography shows the typical inferior steepening of the cornea.

Pellucid marginal degenerationThe topography shows inferior steepening of the cornea, but also shows the typical flattening of the central cornea.

What do you see ?

Increased right corneal diameter

Buphthalmos

There are multiple horizontal lines in the descemet's membrane (Haab's striae).

The cornea may be edematous if there are insufficient endothelium.

What else would you like to do? Look for secondary congenital glaucoma such as

aniridia, anterior chamber cleavage syndrome. Measure the corneal diameter (the normal corneal

diameter is between 10 and 12 mm) with the slit-lamp. Check the corneal edge on the temporal side for

any goniotomy scars. Also look for trabeculectomy scar at the superior

limbus Examine the optic disc for glaucomatous

changes Check the patient's glasses, the affected side

invariably has a myopic prescription.

Causes of congenital glaucoma Primary congenital glaucoma Anterior cleave syndrome (Axenfeld,

Reiger and Peter's syndrome) Rubella Phakomatosis (Sturge-Weber's syndrome

and neurofibromatosis) Aniridia Persistent hyperplastic primary vitreous

Ocular conditions associated with buphthalmos

Myopia Lens subluxation Corneal decompensation Retinal detachment

What do you see ?

There is a band of sub-epithlial whitish depositions in the inter-palpebral zone. It is separated from the limbus by a clear zone. There are multiple round clear holes (due to nerve channels).

Band keratopathy Look for any coexisting corneal lesions

such as interstitial keratitis If the patient is young (especially female)

look for pseudophakia and aqueous haze and signs of arthritis

A unilateral band keratopathy may be caused by a phthisical eye

If the center of the band is clear with well-defined edges, the calcium may have been removed with EDTA or excimer laser.

Causes of band keratopathy? Ocular diseases:

Chronic ocular disease; usually inflammatory (juvenile chronic arthritis)

Phthisis bulbi Interstitial keratitis Silicon oil keratopathy

Systemic hypercalcaemia: Hyperparathryodism Vitamin D toxicity Sarcoidosis

Chronic renal failure Idiopathic

Indications for removingband keratopathy

Cosmesis Visual disturbance Pain from the breakdown of epithelium

Band keratopathy treated withexcimer laser

What do you see ?

The cornea has diffused stromal haze.

High magnification shows ghost (empty) vessels in the deep and mid-stroma. The cornea may be thin. The condition is usually bilateral.

Interstitial Keratitis

Look for Signs of congenital syphilis

Saddle-nose Deafness Under-developed dentition.

Syphilitic keratitis presentation It occurs in congenital syphilis and

usually develops in the first or second decades of life.

It is divided into three stages: Early stage: characterized by ocular pain,

photophobia. There is deep stromal and endothelial edema. KPs may occur.

Florid stage: when the inflammation is at its peak with iridocyclitis. There is deep stromal vessels which gives a pink color to the cornea (salmon pink)

Regression: vascular regression with clearing of the stromal infiltrates leaving behind corneal scarring. This may take up to 1 or 2 years to resolve unless topical steroid is used.

Signs of Hutchinson's triad ?

Saddle-nose Interstitial keratitis Hutchinson's teeth

widely spaced peg-shaped upper incisors Crescentric notch at the cutting edge

What do you see ?

Corneal deposits (basal layer of the epithelium) distributed in whorl's-like pattern

Cornea verticillata

Vortex KeratopathyLook for signs of: Amiodarone intake (for example photosensitivity of

the skin, irregular pulse rate). There may be BRAO or CRAO from emboli)

Indomethacin intake (look for signs of rheumatoid arthritis)

Fabry's disease (renal failure with arterio-venous fistula, angiokeratomas, dilated and tortuous  conjunctival vessels with or without aneurysms)

Fabry's disease ? It is an X-linked disorder due to a

deficiency of alpha-galactosidase. It causes deposition of glycosphingolipid

in the body tissue. Renal involvement causes renal failure. Skin lesion termed angiokeratoma

corporis discusum consists of clusters of superficial cutaneous dark-red angiokeratomas.

Apart from vortex keratopathy, there may be tortuosity and aneurysmal dilatations of the conjunctival and retinal vessels.

Skin lesion in Fabry's disease

Angiokeratoma corporis discusum

What do you see ?

There are multiple sub-epithelial ring-shaped opacities (so called honeycomb appearance) in the center of the cornea 

Opacities may extend towards the periphery in severe cases. The corneal surface is irregular with ferritin deposition.Look at the opposite eye for: Similar changes, corneal graft

Reis-Buckler's dystrophy features? Autosomal dominant Appear in the first few years of life and mainly

affects the Bowman's membrane Symptoms begin in the first or second decade

with painful, recurrent epithelial erosion. Vision is affected by both anterior scarring with

surface irregularity and anterior stromal oedema (from recurrent corneal erosion)

Histologically, there is disruption and absence of Bowman's layer, with replacement by fibrocellular tissue that corresponds clinically to areas of subepithelial opacification.

Keratoplasty is the treatment of choice (either penetrating or lamellar) and recurrence in the graft is common.

What do you see ?

There are refractile, branching lines (in the stroma) The periphery of the cornea is spared. The lines may be double contoured in advanced cases.

Has the highest tendency for recurrence in the graft.

Look for systemic amyloidosis (rare) such as macroglossia and periorbital papules

Periorbital papules seen in amyloidosis

Types of lattice dystrophy?

Type I: Classic type, type AA amyloid No systemic amyloid deposition

Type II: Lattice dystrophy with coexistent systemic amyloidosis lines are less numerous and located more peripherally Known as Meretoja's syndrome. The patient may have

cranial and peripheral neuropathy. Type III:

Mid-stromal and larger deposit than those in type I

Deposits are of type AP amyloid

Histological slide of lattice dystrophy. What stain has been used ?

The cornea is stained with Congo red,and contains multiple reddish deposits representing amyloid deposits.

What do you see ?

There are multiple greyish white opacities involving the stroma and the corneal periphery (in granular and lattice dystrophy, the periphery is typically spared). The stroma between the opacities is diffusely cloudy

Right picture: recipient cornea showing changes of macular dystrophy (because the dystrophy extends to the periphery).

Macular dystrophy-pathogenesis It is a autosomal recessive condition Characterized by an accumulation of

glycosaminoglycan both intra and extracellularly.

It is thought to be caused by defective sulfo-transferase.

It is thought to be a type of localized mucopolysaccharidosis.

Mucopolysaccharidosis It is an inborn error of metabolism

characterized by glycosaminoglycan accumulation.

The condition is usually autosomal recessive except for Hunter's Syndrome which is X-linked.

Most of these patients have ocular involvement which include corneal cloudiness, retinal pigmentary degeneration and optic atrophy.

Visual prognosis for macular dystrophy?

Most patients develop significant visual impairment by the age of 30

Corneal graft is usually necessary to improve vision

Recurrence has been reported in grafted cornea and re-graft is sometimes necessary

Histological slide of macular dystrophy.What stain has been used ?

Macular dystrophy is best shown with alcian blue and colloidal iron. Colloidal iron is used in this case.

What do you see ?

There are multiple small, well-demarcated, grayish white opacities(in the anterior stroma).

The intervening stroma is clear and the peripheral cornea is not involved.

Classically described ‘bread crumbs’, some have crystalline like appearanceThe opposite eye either has similar changes or has corneal graft

Granular dystrophy-features?

It is an autosomal dominant condition. It usually presents in the teens with

photophobia or abnormal corneal appearance.

Recurrent erosion is uncommon. Vision is often normal or only become

impaired in the 40s. Full thickness graft is sometimes needed

but recurrence is unusual.

Histological slide of granular dystrophy.Which stain has been used ?

The cornea has been stained with Masson trichrome which shows up the granular dystrophy as red

There are multiple small white crystals in the center of the cornea (just below the Bowman's membranes)

The surface of the cornea is uninvolved and there may be corneal arcus

Autosomal dominant inheritance

What do you see ?

Schnyder central crystalline dystrophy

There are multiple grayish nebulous opacities separated by crack like clear zones (changes may resemble crocodile shagreen)

The opacities are denser in the center and the posterior aspect of the cornea.

Autosomal dominant inheritance

What do you see ?

Central cloudy dystrophy of Francõis

There are multiple vesicles in the endothelium. There are also multiple greyish opacities which may be curvilinear or has scalloped edges.

In some patients there may be stromal oedema or abnormal iris shape such as corectopia  or irido-corneal adhesion (the changes may resemble ICE syndrome but the condition is bilateral)

Autosomal dominant inheritance

What do you see ?

Posterior polymorphous endothelial dystrophy

There are multiple opacities in the epithelium and has shapes resembling map lines, dots/microcysts or fingerprint lines

Common condition Dominant

inheritance with incomplete penetrance

What do you see ?

Map-dot-fingerprint dystrophy (Cogan microcystic dystrophy)

Endothelial dystrophies They can all present with endothelial failure with

corneal edema. Fuchs' endothelial dystrophy: autosomal

dominant; usually present in the 5th-6th decade with corneal edema

Posterior polymorphous dystrophy: autosomal dominant; most patients are asymptomatic but in some there may be corneal edema. The trabecular meshwork and the iris may be involved by the abnormal endothelium giving rise to glaucoma and abnormal iris shapes

Congenital hereditary endothelial dystrophy: may be autosomal dominant or recessive. The recessive form is associated with severe corneal edema at birth.

What do you see ?

There are radial incisions (usually four or eight) in the cornea with a clear central zone. There may be ferritin lines at or around the incisions.

How does radial keratotomy correct myopia ?

Radial incisions (up to a depth of 90%) causes flattening of the cornea and reduces the radius of curvature of the cornea. This procedure weakens the cornea and trauma to the eye can easily cause.

The amount of correction (i.e. the refractive effect) is determined by the depth, length and number of cuts.

What do you see ?

Typical facial feature in acne rosacea Cornea neovascularization in rosacea keratitis

Acne rosacea

The face is red with telangiectasia, papules and pustules found mainly on the nose, cheeks and chin. The nose may have irregular thickening of the skin with large follicular orifices (rhinophyma). Look for: Blepharitis, meibomian gland dysfunction, keratitis.

Rosacea keratitis

Acne rosacea is a common skin condition of unknown origin.

Ocular involvement is common but most tend to be mild.

Ocular problems is more severe in males Eyelids show blepharo-conjunctivitis sometimes

with thick meibomian secretion (chalazion may be present)

There may be scars on the tarsal conjunctiva suggesting previous recurrent chalazion.

The cornea show pannus with or without peripheral corneal thinning.

There are subepithelial opacities especially inferiorly

How would you manage the ocular problem of acne rosacea ?

The lid problems include blepharitis and chronic meibomian inflammation. Lid hygiene and hot compresses are needed to keep

the lids comfortable. In severe cases, oral doxycycline is useful for a period

of 6 weeks but some patients may need the treatment for much longer.

The cornea problems are related to dry eyes, neovascularization and peripheral ulceration. Dry eyes can be controlled with lid hygiene and

artificial tears. Neovascularization results from chronic corneal

inflammation, and low dose steroid is useful but should be used with care due to the risk of perforation.

Peripheral ulceration may result from Staphylococcal hypersensitivity and the treatment involve lid hygiene and low dose combination of steroid and antibiotic.

Doxycycline/tetracycline has the tendency for binding to growing structures that require calcification (chiefly teeth and bones). These can result in unsightly staining of the teeth, dental hypoplasia and bone mal-development.

Doxycycline/tetracycline should be avoided in pregnant women and young children. It is also contraindicated in breast feeding women as the drug is secreted in breast milk.

A 3-month pregnant female develops severe blepharitis and keratitis secondary to acne rosacea. How would you treat her ?

What do you see ?

A penetrating corneal graft with interrupted sutures

A tectonic graft

performed for peripheral corneal perforation resulting from rheumatoid arthritis-related corneal melt

Check the graft for: Penetrating or lamellar graft (look at the edge of

the graft for the thickness) The sutures are interrupted / continuous or a

combination of both Is the graft eccentric (it is likely to be tectonic) Signs of rejection which may be:

Epithelial, stromal or endothelial. Rejection lines on the endothelium are called

Khodadoust's line. keratic precipitates, cells or flare in the anterior

chamber Security of the suture and any pannus around

the sutures

Look for the cause for the graft:

Presence of IOL especially anterior chamber lens suggest pseudophakic bullous keratopathy

Look at the recipient cornea for signs for corneal dystrophy (this is especially obvious with macular dystrophy which extend to the peripheral cornea)

Examine the other eye for signs of dystrophies or keratoconus.

In tectonic graft observe the patient's hands for rheumatoid arthritis which may be the cause of peripheral corneal melt

Post-operative complications of corneal graft?

Problems related to surgery and sutures Non-immune corneal problems Graft rejection

Problems related to surgery and sutures

Wound leak: Resuturing, patching or contact lenses

Flat chamber/iris incarceration in the wound: Poor integrity of the wound or high IOP Early surgical intervention is important

Endophthalmitis: Paracentesis and vitreous tap for culture and sensitivity followed by intravitreous antibiotic with amikacin and

vancomycin Suture-related problems:

Tightening, loosening, infectious abscesses and vascularization along suture tracks etc.

The sutures are removed and appropriate treatment given

Non-immune corneal problems Primary endothelial failure:

From deficiency of donor endothelium or the cornea is sutured with the endothelium side up by mistake.

Re-graft is the only option Persistent epithelial defect:

This usually heal by 14 days. Treat any dry eyes, exposure keratitis or trichiasis

Recurrence of primary disease: Treat conditions such as herpes keratitis as appropriate

Infectious keratitis: Intensive topical antibiotics are needed

Late non-immune endothelial failure: Re-graft is needed

Post-operative corneal astigmatism: Removal of the offending sutures and consider CL Refractive surgery may be needed

Graft rejection Usually occurs after the first two weeks and

early recognition is important for good outcome Endothelial rejection is the most serious.

Keratic precipitates and Khodadoust's lines may be seen.

Patient should be admitted for intensive topical steroids.

Subepithelial infiltrates May resemble adenoviral infection, may be directed at

the donor epithelium or keratocytes and may precede more serious rejection

Topical steroid is the treatment of choice. Donor epithelium may be rejected showing as a

rejection line. As the host cells replace lost donor epithelium, this

rejection is less serious than endothelium rejection but it may precede endothelium rejection.

Storage of donor corneas in eye banks ? The two main methods of storing are by Refrigeration

4°C (USA) in Organ culture at 31-37°C (Europe).longer storage timeGreater opportunity to detect infectionReduced risk of Post-op endophthalmitis

(20-fold less) Eyes are first washed in several changes of sterile saline,

immersed in a dilute iodine solution, which is neutralized with sodium thiosulphate, and then given a final wash in saline.

The cornea with a 3-4mm rim of sclera is then carefully excised taking care to avoid damage to the endothelium.

A suture is placed through the scleral rim and the cornea is suspended in about 80-ml of tissue culture medium.

The corneas are then stored in an incubator. After a week, a sample of medium is withdrawn to check

for bacterial and fungal infection. Up to 4% of corneas are discarded for this reason.

Corneal assessment before being used for graft ?

The quality of the tissue is assessed, primarily by examination of the endothelium to estimate endothelial cell density and to detect endothelial damage or other abnormalities.

A minimum cell density of 2200 cells/mm2 with no central stromal opacity is considered acceptable for penetrating grafts.

This quality assessment means that no age limits to corneal donation need be set.

Because corneas become edematous and thickened during organ culture, they are transferred to tissue culture medium containing 5% dextran after assessment of the endothelium. The osmotic effect of the dextran thins the cornea and returns it towards normal thickness prior to surgery. The corneas can remain in this medium for four days by which time they would have been transported to a recipient hospital and grafted.

Corneas are tested for????

What do you See ?• There is are peripheral

thinning of the superior cornea which has a sloping peripherally and a sharp central edge

• Usually bilateral but asymmetrical

• The epithelium is intact and contains superficial vascularization.

• There may be pseudo-pterygium in advanced cases. Terrien's marginal

degeneration

Does Terrien's marginal degeneration ever affect the vision ? Although usually asymptomatic,

advanced cases may affect the vision by causing astigmatism which is usually against the rule.

There is also the risk of corneal perforation with minor trauma

What do you See ?• There is thinning with

ulceration involving a sector of the peripheral cornea.

• Look for: • Associated systemic signs

such as symmetrical arthropathy in rheumatoid arthritis or saddle nose in Wegener's granulomatosis

• Associated eye signs such as keratoconjunctiva sicca or scleromalacia perforan both of which may occur in rheumatoid arthritis

Peripheral corneal ulceration due to systemic diseases

What systemic conditions may be associated with peripheral corneal ulceration ?

Rheumatoid arthritis Wegener's granulomatosis SLE Inflammatory bowel diseases Polyarteritis nodosa Acne rosacea Leukemia

What do you See ?• There is peripheral

ulcerative keratitis which is contiguous with the limbus without intervening clear zone.

• The epithelium is vascularized and there is an overhanging advancing edge.

• The whole corneal circumference may be involved.

• The sclera is not involved.Mooren's ulcer

How do you diagnose Mooren‘s ulcer?

The diagnosis is based on the clinical history and characteristic appearance in conjunction with the exclusion of other causes of peripheral ulcerative keratitis.

There are no histological or blood tests for its diagnosis.

What do you see ? There is a prominent

irregular ridge which lies central to the limbus.

It is caused by an anteriorly  displaced Schwalbe's line. (junction of the TM with the termination of Descemet's membrane

Note: this finding is seen in about 8 to 30% of normal individual.

Look for other pathology !

Posterior embryotoxon

What do you see ? There is posterior embryotoxon

with iris strands attached to it. Peripheral anterior synechiae and hypoplasia of the  anterior stroma may be seen. 

Axenfeld's anomaly have posterior embryotoxon plus anterior synechiae

Reiger's anomaly have posterior embryotoxon, anterior synechiae, iris atrophy and pupil distortion

Reiger's syndrome is Reiger's anomaly plus dental, craniofacial and skeletal abnormalities.Look for:

Trabeculectomy  Corectopia, ectopia uvea and

polycoria Abnormal denture and maxillary

hypoplasia Axenfeld-Reiger's syndrome

Dental dysplasia in a patient with Axenfeld-Reiger's syndrome

What do you see ? There is central corneal

opacity involving the stroma with iris adhesion at the edges of the opacities.  Look for: Trabeculectomy  Small eye

(microphthalmos) Cleft lip/palate,

craniofacial anomalies Skeletal abnormalities Evidence of congenital

cardiac defects (if any of these were

present, the condition is called Peters plus syndrome) Peters' anomaly

How are the above conditions inherited ?

Posterior embryotoxon and Axenfeld-Reiger's syndrome are usually inherited in an autosomal dominant fashion.

Peters' anomaly may be sporadic, recessive and sometimes dominant.

What is the incidence of glaucoma in the above conditions ?

Posterior embryotoxon alone is not associated with glaucoma.

50% of the patients with Axenfeld-Reiger's syndrome and Peters' anomaly will develop glaucoma.

What does the mnemonic STUMPED stands for in a patient with a congenitally opaque cornea ?

S Sclero-cornea T Trauma U Ulcers (e.g. herpes simplex) M Metabolic disorders (e.g. MPS) P Peters' anomaly E Endothelial dystrophy (e.g. CHED) D Dermoid