Dystrophies

Question 1

Reis buckler and Thiel -Behnke

Answer 1

AD
BOTH caused by mutations in TGFBI gene = abnormal version of keratoepithelin = affect Bowman’s layer. SPARES PERIPHERY.

Bowman’s layer replaced by fibrocellular material = “saw tooth” with honeycomb opacities at Bowman layer (pathognomonic for Thiel-Behnke)

Can only differentiate Thiel-Behnke (“curly fibers”) vs. Reis-Buckler (none) on EM. TB is more mild.

Recurrent erosions more common in Reis Buckler (Reis = Recurrent). Masson trichrome for Reis Buckler.

Mnemonic: Dr. Boehlke wears a Mason buckle which erodes through. He is dominant at surgery (AD & “saw-tooth”) and has curly hair, but it is more mild than Mason buckle.

Question 2

Gelatinous droplike dystrophy

Answer 2

AR, mutation in tumor associated calcium signal transducer 2 gene. found mostly in Japanese patients

Onset = teens-twenties

Initally: may resemble band keratopathy. On light microscopy: diffuse subepithelial and stromal AMYLOID deposits

eventually: lesions look like “mulberries”

Recurrence rate: virtually 100% after PK

Question 3

Age of presentation of dystrophies

Answer 3

My Little Granny (is the oldest)
Macular (youngest)
Lattice
Granny (oldest)

Question 4

Megalocornea associated with what conditions. Inheritance?

Answer 4

XR, nonprogressive and BILATERAL.
Histologically normal Ks with horizontal diameter > 13 mm

may have glaucoma (BUT NOT CONGENITAL)
assoc/w/Marfans

Question 5

Pellucid marginal degeneration area of thinning and protrusion

Answer 5

Bilateral ectasia.
BAND OF THINNING (~1-2 mm) in INFERIOR cornea from 4:00 to 8:00

“Crab claw” = shift FROM ATR (superiorly) to WTR (inferiorly)

Protrusion of cornea is seen ABOVE area of thinning (unlike keratoconus, where protrusion is WITHIN the area of thinning)

Question 6

ABMD Rx

Answer 6

1) conservative: hypertonic saline gtts and/or BCL
2) epithelial debridement first line, then consider anterior stromal micropuncture or PTK

Recurrent errosions 2/2 shearing injury = more amendable to anterior stromal micropuncture (use 25 g needle)

Question 7

Central cloudy dystrophy of francois

Answer 7

-diamond shaped opacities with clear intervening spaces (present at birth)

In DDx: posterior crocodile shagreen but develops in older age 2/2 degeneration

Question 8

PPMD and ICE

Answer 8

both may have iris atrophy, corectopia and PAS

PPMD (b/L & AD), ICE (sporadic and u/L)

Question 9

Least common stromal dystrophy

Answer 9

Little Green Men
Lattice recurs/occurs the MOST

Macular (least common K stromal dystrophy)
Granula
Lattice (most common, also recurs the most)

MC K dystrophy = EBMD

Question 10

Munson sign

Answer 10

cone is juxtaposed against lower eyelid when pt looks down.

Keratoconus (assoc/w/ eye rubbing and atopy)

Question 11

Fabry disease

Answer 11

XR (“fabulous hunter”)

sphingolipiodses (other two main types: multiple sulfatase deficiency, generalized gangliosidosis). All have corneal verticillata.

Fabry - also have renal failure and peripheral neuropathy

Question 12

Bietti corneoretinal dystrophy

Answer 12

Progressive NIGHT blindness
Visual field loss
Ocular irritation or photophobia

Slit-lamp exam: sparkling yellow-white crystals mostly in PERIPHERAL stroma; tiny, yellowish retinal crystals (tapetoretinal dystrophy)

2/2 defect in lipid metabolism

No Rx
Mnemonic: BNVP - Best (bietti) night fatty VP (lipid mtb problem/visual field loss/photophobia)

Question 13

Cystinosis

Answer 13

AR
most common in French-speaking Canada
Obtain history for age of onset
Determine presence of renal disease (polyuria/polydipsia)
Ocular irritation or photophobia

Slit-lamp exam: polychromatic cystine crystals in the conjunctiva, anterior stroma as early as 1 yo
Gonioscopy: cystine crystals in trabecular meshwork
Workup: check leukocyte cystine level and/or document evidence of cystine crystal formation in the cornea

Cysteamine eyedrops for corneal deposits
Oral form for systemic disease

3 main clinical forms of cystinosis depending on age of presentation: (MC =) infantile, adolescent, and adult. The infantile form is the most common
patients with severe renal impairment (nephrotic form), patchy depigmentation of the RPE can occur. This generally does not lead to a loss in vision.

Question 14

Lisch epithelial corneal dystrophy (LECD)

Answer 14

X-rated Dominant.
usually presents in childhood with densely crowded gray opacities and microcysts in the epithelium arranged in feathery, radial, flame-shaped, band-shaped, or whorl-like patterns

only known corneal epithelial dystrophy with X-chromosomal dominant inheritance.

The opacities can progress to produce vision loss. Debridement of the corneal epithelium does not prevent the opacities from recurring, but rigid contact lenses have been shown to lessen the number of opacities in some patients.

Question 15

Meesmann corneal dystrophy (MCED)

Answer 15

AD - mutation in KRT3 or KRT12 (corneal keratin)
dz of K epi and basement membrane.
early onset: infancy or early childhood. progresses slowly and is often asymptomatic until middle age.

dystrophy characterized by numerous tiny gray EPITHELIAL VESICLES (retroillumination) that extend to the limbus but are OFTEN DENSER IN THE INTERPALPEBRAL ZONE. Can almost look like SEI on SLE photo.
“Peculiar substance” – fibrogranular material surround by tangles of cytoplasmic filaments –> cell death. Normal stroma/endothelium

Sx: mild ocular irritation and light sensitivity; some patients experience blurred vision due to corneal surface irregularity and scarring from erupted vesicles.

Stocker-Holt variant of MCED presents with more severe Si/Sx, as well as fine, punctate epithelial opacities that stain with fluorescein and infrequent linear opacities in whorl-like patterns.

Rx: depends on severity, and can include lubricants, therapeutic contacts, epithelial debridement, PTK and lamellar keratoplasty (LK).

Mnemonic: MAD peculiar epi. Messeman AD pecular substance epithelium

Question 16

Posterior polymorphous dystrophy (PPMD)

Answer 16

rare, autosomal dominant disorder that is typically asymptomatic. It is characterized by three distinct patterns of posterior corneal findings: (1) a cluster or linear arrangement of vesicles in the posterior cornea surrounded by a gray haze; (2) band lesions; and (3) diffuse opacities. Glaucoma occurs in 10-15% of patients with PPMD. Its phenotype can vary widely with some affected individuals progressing to corneal decompensation, having broad peripheral synechiae, or progressing to advanced glaucoma.

Like the ICE syndromes, it may have iris atrophy, corectopia, and iridocorneal adhesions. Unlike the ICE syndromes which are unilateral, PPMD is bilateral although it can be highly asymmetric. ICE syndromes are also sporadic without any known inheritance pattern.

Bottom line: PPMD –> vesicles of posterior cornea + glaucoma in some cases + bilateral + autosomal dominant.

Both ICE and PPMD are diseases where the endothelium acts like epithelium. The difference is that PPMD is a dystrophy and is therefore bilateral. ICE syndrome is unilateral. PPMD is also autosomal dominant so often there is a family history. ICE syndrome is not inherited.

characterized by the presence of multilayer endothelial cells that look and behave like epithelial cells.

Question 17

Posterior amorphous corneal dystrophy

Answer 17

AD
is a rare stromal dystrophy that manifests as diffuse grey-white sheetlike stromal opacities concentrated in the posterior stroma. Descemet’s membrane can be involved with focal areas of endothelial disruption.

tend to have flat and thin corneas which lead to hyperopia. There is NO increase in glaucoma rates.
presents in the first decade of life as a sheet-like opacity in the posterior cornea.
These patients tend to have only minimal loss in vision (usually don’t need K transplant)

Question 18

Fleck dystrophy

Answer 18

AD. It is characterized by dandruff-like deposits throughout the stroma but sparing the epithelium, Bowman layer, Descemet’s membrane, and endothelium.

no VA decline
non-progressive and can be highly-asymmetric or even unilateral.

Question 19

Fabry vs Hunter

Answer 19

both XR. This can be remembered by imagining a “FABulous HUNTER”aiming a bow and arrow at a target shaped like an “X”.

Hunter syndrome = pigmentary retinopathy

Fabry disease are corneal verticillata, periorbital edema, posterior spokelike cataracts, comma-shaped conjunctival aneurysms, macular edema, and retinal vessel dilation.

Question 20

Lowe’s

Answer 20

Lowe’s = think of Lowe’s the store with a crossed off like an X, It is X-linked
Think of Calvin peeing (showing you his posterior; with posterior lenticonus), it involves the renal system.

Question 21

Normal K is flatter where?

Answer 21

Normal K = flatter nasally (think Voldemort is flatter nasally)

Question 22

CHED

Answer 22

two forms of CHED: types 1 and 2.

CHED 1 
Think first place, you dominate (AD)
Can't win with nystagmus (so it doesn't have nystagmus b/c clear at birth)
Painful b/c it takes pain to succeed
Si/Sx @ age 1-2 yo, progressive.

CHED 2 = MC/AR
present at birth and does not get worse and is therefore called “stationary”. The child develops nystagmus because there is no visual sensory input from birth.

In both types of CHED, the cornea has a blue tint because of its marked thickening.

CHED 1 you only need ONE allele, is the dominant version.
CHED 2 you need TWO alleles, is the recessive version.

Question 23

macular corneal dystrophy (MCD)

Answer 23

focal, gray-white stromal opacities with intervening spaces THAT ARE NOT COMPLETELY CLEAR
least common of the corneal stromal dystrophies
gray opacities would extend from limbus-to-limbus which is a feature that does not occur with either lattice or granular dystrophies.

AR
carbohydrate sulfotransferase 6 (CHST6) gene (chromosome 16).

An ELISA test for sulfated keratan sulfate can be used to assist in the diagnosis of MCD even in individuals in the preclinical state.

Of the corneal stromal dystrophies, the age of presentation is the youngest in macular dystrophy followed by lattice and then granular dystrophy. MCD is caused by a defect in carbohydrate sulfotransferase 6 (CHST6).

Question 24

M/G/L differentiating

Answer 24

Lattice spares periphery. Don’t forget about Meretoja

Granular spares 1 mm periphery (helps diistinguish from macular)

Avellino - mix between lattice and granular

Macular = AUTOSOMAL RECESSIVE. extends all the way to the periphery