Flashcards in Genetics Deck (45):
Juvenile-onset glaucoma: GLC1A (aka MYOC)
Pseudoexfoliation glaucoma: LOXL1
Normal tension glaucoma: OPTN
-usually sporadic but assoc/w/CYP1B1
*encodes a protein in the cytochrome P450 enzyme family. Other causative mutations = GLC3A, GLC3B and GLC3C genes.
"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
presents in middle-age adults and can be
Glaucoma (50% in A-R syndrome)
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
Posterior polymorphous dystrophy (PPMD)
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
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.
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.
Pseudoexfoliation Syndrome (PXF) Signs?
Sampolesi’s line (angle)
Patchy TIDs near margin
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
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)
Pseudoexfoliation Syndrome (PXF) Gene association?
LOXL1 (99% of PXF pts, but 80% normal pts)
Disorder of basement membrane
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
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
Pigment Dispersion Syndrome (PDS) Treatment?
SLT bad (IOP spike; use lower power)
How to distinguish ACG from OAG with narrow angles?
Miotic (a blocker) that relieves ACG, but doesn’t reduce IOP or contract ciliary body
Primary Angle Closure Glaucoma Risk factors?
F>M, old age (55-65)
Hyperopia / small eyes
Race (Canadian, Alaskan, Greenland Eskimos, Asians)
Primary Angle Closure Glaucoma Signs?
SLE - Van Herrick, Shaffer (IV = open), Spaeth (D45r = open)
UBM (lower wavelength than B-scan)
Glaukomflecken (sign of past ACG)
Primary Angle Closure Glaucoma Treatment?
LPI (argon vs. YAG)
Argon: 0.02-0.1sec, 50um spot, 800-1000mW
YAG: fewer applications, more bleeding, less histological damage, less iritis
Secondary ACG Iris vs. Lens
1. IRIS - Plateau Iris Syndrome
Secondary ACG Anterior “Pulling”
3. Anterior “Pulling”:
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)
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)
Plateau Iris Syndrome
No improvement with LPI
Gonioplasty (laser peripheral iridoplasty)
Long-term miotic (Pilocarpine 1%)
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
Three types of ICE?
1) Iris nevus (Cogan-Reese)
Pigmented tan iris nodules
Less iris atrophy than latter type
2) Chandler syndrome
Corneal findings predominate
3) Essential iris atrophy
Iris atrophy, corectopia, polycoria, high PAS, heterochromia, ectropion uveae
a.k.a. ciliary block; post. aqueous diversion
Usually complication of filtration surgery in patient with narrow angles
Cycloplegics; NOT pilocarpine
Laser to anterior vitreous face
Vitrectomy + LPI
~50% success with medical tx
Autoimmunity to lens antigens from disrupted lens capsule (surgical or traumatic)
IOP usually normal
Removal of lens fragments
HMW lens proteins leak across intact lens capsule
“Lytic” usu. means macrophages (phacolytic, hemolytic, melanocytomalytic)
Fuchs Heterochromic Iridocyclitis (FHI)
Diffuse iris atrophy
Affected eye hypochromic, except blue iris (heterochromia inversa)
Fine stellate KP
Associated with CR scars
Fine irregular vessels crossing scleral spur
Usually not needed
Poor response to steroids
Self-limited trabeculitis lasting hours-days, but recurrent
Unilateral mild sudden iritis
Very high IOP
Normal optic discs and VF
DDx: HSV trabeculitis
Increased risk for POAG
Horner syndrome (congenital)
Usually due to birth trauma to brachial plexus
Fuchs heterochromic iridocyclitis
Hypertelorism; wide nose bridge
White forelock; poliosis
Hypomelanosis of Ito
Iris ectropion syndrome
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
What med may prevent hyphema re-bleeding?
Occurs after VH or hyphema
Hb-laden macrophages clog angle
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)
Ciliary circular and longitudinal MUSCLE FIBERS separate
Occurs in 60-90% of trauma pts
5% progress to glaucoma (vs 1% normal population)
Ciliary BODY torn from sclera
Hypotony, but rapid IOP rise when close
Most likely site of scleral rupture after open globe from blunt trauma?
Near muscle insertion
Congenital glaucoma (age <3 months)
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
Goniotomy ab interno if cornea clear
Trabeculotomy ab externo if cornea not clear or goniotomy failed
Corneal enlargement DDx?
Cornea sign from birth trauma?
Vertical Descemet’s tears
OS affected more often than OD
Posterior embryotoxon + iris processes to Schwalbe’s line
50% develop glaucoma
Axenfeld + pigmentary retinopathy, corectopia, esotropia, ONH drusen, cholestasis/jaundice, congenital heart dx, flattened facies, bony abnoralities
Axenfeld + iris hypoplasia / holes
50% develop glaucoma
Rieger’s anomaly + systemic:
Mental retardation, dental, craniofacial (maxillary hypoplasia), skeletal anomalies, pituitary abnormalities, hypospadias, loss of DTRs
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