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Glaucoma > Genetics > Flashcards

Flashcards in Genetics Deck (45):
1

Genes

Juvenile-onset glaucoma: GLC1A (aka MYOC)
Pseudoexfoliation glaucoma: LOXL1
Normal tension glaucoma: OPTN


congenital glaucoma
-usually sporadic but assoc/w/CYP1B1

*encodes a protein in the cytochrome P450 enzyme family. Other causative mutations = GLC3A, GLC3B and GLC3C genes.

2

"Axenfeld-Rieger syndrome" (A-R syndrome) vs ICE

A-R syndrome = hereditary (usually AD), bilateral, not associated with corneal endothelial changes or edema, presents at a young age
posterior embryotoxon (i.e. prominent Schwalbe's line),
associated with systemic signs (e.g. hypodontia, maxillary hypoplasia, redundant periumbilical skin).

ICE = sporadic inheritance
u/L
presents in middle-age adults and can be

Both:
Corectopia
Glaucoma (50% in A-R syndrome)

2

NTG vs POAG

Though there is considerable debate on whether NTG is truly a distinct entity from POAG, most experts agree that the following features are more characteristic of NTG:


Increased frequency of disc hemorrhages. These splinter hemorrhages tend to occur in the upper and lower poles of the optic disc (especially inferotemporally).
More prominent peripapillary atrophy
More prominent disc notching
More disc sloping
Larger optic disc size
Visual field defects that are deeper and closer to fixation

3

Posterior polymorphous dystrophy (PPMD)

rare
AD
typically asymptomatic
bilateral although it can be highly asymmetric.

three distinct patterns of posterior corneal findings:
(1) a cluster or linear arrangement of vesicles in the posterior cornea surrounded by a gray haze (as seen in the photo above);
(2) band lesions
(3) diffuse opacities

Glaucoma (10-15%)
Like the ICE syndromes, it may have iris atrophy, corectopia, and iridocorneal adhesions.

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

4

Congenital glaucoma RX

In contrast to glaucoma in adults, surgical treatment is usually the initial/definitive treatment of choice for congenital glaucomas. Medical therapy should only be used in the short term while awaiting definitive surgical treatment for these infants.

The two classic treatments for congenital glaucoma are goniotomy and trabeculotomy. If the angle can be clearly visualized (i.e. clear cornea), then a goniotomy is typically performed first. If the cornea is too cloudy to visualize the angle properly, then a trabeculotomy is performed.

Subsequent procedures include additional goniotomies or trabeculotomies followed by either trabeculectomy or a glaucoma drainage implant.

5

Pseudoexfoliation Syndrome (PXF) Signs?

Sampolesi’s line (angle)
Patchy TIDs near margin
Weak zonules
Poor dilation

6

Pseudoexfoliation Syndrome (PXF) demographics?

Elderly Russian man with phacodonesis
Exfoliation material in anterior segment
M=F, usu. >age 60, N. Europeans
>50% OAG in Scandinavian countries

7

Components of PXF material?

Components of PXF material?
HSPG, CSPG, Collagen type IV, laminin, fibillin, amyloid P, cathepsin B (lysosomal enz)

Distinguished from true exfoliation from infrared radiation (welder)

8

Pseudoexfoliation Syndrome (PXF) Gene association?

LOXL1 (99% of PXF pts, but 80% normal pts)
Disorder of basement membrane

9

Pigment Dispersion Syndrome (PDS) demographics?

Young, myopic man blurred in exercise
Chafing from iris pigment epithelium
M>F, young adults, myopic>emmetropic
30-50% develop glaucoma

Myopic: increased risk of retinal breaks

10

Pigment Dispersion Syndrome (PDS) Signs?

Krukenberg spindle (cornea)
Scheie stripe (post. capsule)
Zentmayer line (ant hyaloid, zonular fibers)
Concave iris + mid-peripheral slit-like TIDs
Pigment in angle
Wide IOP fluctuations

11

Pigment Dispersion Syndrome (PDS) Treatment?

Miotics
LPI unproven
ALT good
SLT bad (IOP spike; use lower power)

12

How to distinguish ACG from OAG with narrow angles?

Thymoxamine test
Miotic (a blocker) that relieves ACG, but doesn’t reduce IOP or contract ciliary body

13

Primary Angle Closure Glaucoma Risk factors?

F>M, old age (55-65)
Hyperopia / small eyes
Race (Canadian, Alaskan, Greenland Eskimos, Asians)

14

Primary Angle Closure Glaucoma Signs?

Narrow angles
SLE - Van Herrick, Shaffer (IV = open), Spaeth (D45r = open)
UBM (lower wavelength than B-scan)
Glaukomflecken (sign of past ACG)

15

Primary Angle Closure Glaucoma Treatment?

Medications
Cataract extraction
LPI (argon vs. YAG)
YAG: 2-8mJ
Argon: 0.02-0.1sec, 50um spot, 800-1000mW
YAG: fewer applications, more bleeding, less histological damage, less iritis

16

Secondary ACG Iris vs. Lens

1. IRIS - Plateau Iris Syndrome

2. Lens:
Phacomorphic Glaucoma
Lens dislocation

17

Secondary ACG Anterior “Pulling”

3. Anterior “Pulling”:
ICE syndrome
Epithelial downgrowth
Synechial chronic ACG
NVG (open + closed angle)
NVA stops at Schwalbe’s line unless bad cornea (e.g. ICE)
Adults (PDR, CRVO – 10% NVA); Children (RB)

18

Secondary ACG Posterior “Pushing”:

4. Posterior “Pushing”:
Malignant glaucoma / aqueous misdirection
Tight scleral buckle – causes CB rotation & inflammation
Uveal effusion – (e.g. nanophthalmos, topiramate)
Exudative RD, tumor – (e.g. ciliary body melanoma)

19

Plateau Iris Syndrome

No improvement with LPI

Treatment?
Gonioplasty (laser peripheral iridoplasty)
Long-term miotic (Pilocarpine 1%)

20

ICE Syndrome (Irido-corneal Endothelial Syndrome)

Abnormal proliferation of corneal endothelium (act like epithelial cells)
Cells cover angle causing glaucoma
May develop high PAS + angle closure
Unilateral, middle-age adults, females, NOT familial
Corneal endothelium has beaten bronze appearance
Spectral microscopy shows fewer cells with dark centers (light in PPMD)


Treatment: PKP treats corneal component, meds or surgery for glaucoma

21

Three types of ICE?

1) Iris nevus (Cogan-Reese)
Pigmented tan iris nodules
Less iris atrophy than latter type

2) Chandler syndrome
Corneal edema
Corneal findings predominate
Most common

3) Essential iris atrophy
Iris atrophy, corectopia, polycoria, high PAS, heterochromia, ectropion uveae

22

Aqueous Misdirection

a.k.a. ciliary block; post. aqueous diversion

Cause?
Usually complication of filtration surgery in patient with narrow angles

Treatment?
Aqueous suppressants
Cycloplegics; NOT pilocarpine
Laser to anterior vitreous face
Vitrectomy + LPI
~50% success with medical tx

23

Phacoantigenic

Autoimmunity to lens antigens from disrupted lens capsule (surgical or traumatic)

Signs?
+KP
IOP usually normal
Pathological findings?

Zonal granuloma
(Ag/PMN/multinucGC/mono)

Treatment?
Steroids
Mydriatic
Removal of lens fragments

24

Phacolytic

HMW lens proteins leak across intact lens capsule

Signs?
No KP
Iridescent particles

Pathological findings?
Lens-laden macrophages
“Lytic” usu. means macrophages (phacolytic, hemolytic, melanocytomalytic)

Treatment?
Cataract Surgery

25

Fuchs Heterochromic Iridocyclitis (FHI)

Unilateral

Findings?
Diffuse iris atrophy
Affected eye hypochromic, except blue iris (heterochromia inversa)
Fine stellate KP
Minimal cell/flare
Synechiae rare
Cataract/glaucoma common
Associated with CR scars

On gonioscopy?
Fine irregular vessels crossing scleral spur

Treatment?
Usually not needed
Poor response to steroids

26

Posner-Schlossman Syndrome

Glaucomatocyclitic crisis
Self-limited trabeculitis lasting hours-days, but recurrent
Unilateral mild sudden iritis

Findings?
Very high IOP
Microcystic edema
Fine KP
Normal optic discs and VF
DDx: HSV trabeculitis
Increased risk for POAG
HLA association?
HLA-B54

Treatment?
Steroids, NSAIDs
Anti-hypertensives

27

Hypochromic

Horner syndrome (congenital)
Usually due to birth trauma to brachial plexus
Incontinentia pigmenti
Fuchs heterochromic iridocyclitis
Waardenburg-Klein syndrome
Hypertelorism; wide nose bridge
Cochlear deafness
White forelock; poliosis
Nonpigmented tumors
Hypomelanosis of Ito
JXG

28

Hyperchromic

Oculodermal melanocytosis
Pigmented tumors
Siderosis
Iris ectropion syndrome
Extensive rubeosis

29

Hyphema When to go to surgery (AC Washout)?

When to go to surgery (AC Washout)?
IOP>50 for >3 days
IOP>35 for >7 days
Total hyphema > 9 days
Sickle cell dx (IOP >25 for >24hrs)
Sickle trait debatable
Corneal blood staining

30

What med may prevent hyphema re-bleeding?

Aminocaproic acid

31

Hemolytic glaucoma

Occurs after VH or hyphema
Hb-laden macrophages clog angle

32

Ghost cell glaucoma

Occurs 1-3mo after VH
Khaki-colored ghost cells clog angle
Pseudohypopyon with candy-stripe pattern of layered RBC w/ ghost cells
Heinz bodies (clumps of denatured Hb)
Treatment: washout, vitrectomy (definitive)

33

Angle Recession

Ciliary circular and longitudinal MUSCLE FIBERS separate
Occurs in 60-90% of trauma pts
5% progress to glaucoma (vs 1% normal population)

34

Cyclodialysis cleft

Ciliary BODY torn from sclera
Hypotony, but rapid IOP rise when close

35

Most likely site of scleral rupture after open globe from blunt trauma?

Superonasal quadrant
Near muscle insertion
At equator

36

Congenital glaucoma (age <3 months)

2/3 boys
2/3 bilateral

Symptoms?
Blepharospasm
Epiphora
Photophobia

Corneal sign?
Haab’s striae (horizontal)
Infantile (age 3 months - 3 years)
Juvenile (age 3 - 35 years)
Cupping is reversible in childhood
Gonio landmarks obscured by Barkan’s membrane, can be incised in goniotomy

Treatment?
Goniotomy ab interno if cornea clear
Trabeculotomy ab externo if cornea not clear or goniotomy failed

37

Corneal enlargement DDx?

Congenital glaucoma
X-linked megalocornea
High myopia
Exophthalmos

38

Cornea sign from birth trauma?

Vertical Descemet’s tears
OS affected more often than OD

39

Axenfeld’s anomaly:

Posterior embryotoxon + iris processes to Schwalbe’s line
50% develop glaucoma

40

Alagille syndrome:

Axenfeld + pigmentary retinopathy, corectopia, esotropia, ONH drusen, cholestasis/jaundice, congenital heart dx, flattened facies, bony abnoralities

41

Rieger’s anomaly:

Axenfeld + iris hypoplasia / holes
50% develop glaucoma

42

Rieger’s syndrome:

Rieger’s anomaly + systemic:
Mental retardation, dental, craniofacial (maxillary hypoplasia), skeletal anomalies, pituitary abnormalities, hypospadias, loss of DTRs

43

Aniridia

85% familial (PAX6; AD)
13% sporadic, associated w/ WAGR (sporadic associated with large chromosomal deletions)
Wilm’s Tumor, Aniridia, Genitourinary, Retardation
2% Gillespie syndrome (AR)
MR + cerebellar ataxia
50-75% develop glaucoma

44

Peter’s Anomaly

Progressive central leukoma with clear periphery
Absent Descemet’s + endothelium with iris adhesions
Sporadic; 60% bilateral
50% develop glaucoma

Peters’ Plus (60% w/ systemic sx):
cardiac, craniofacial, skeletal anomalies