Transcript 2015_03_20-Axenfeld-Rieger-ReemaSyedx

Grand Rounds Conference
Reema Syed, MBBS
University of Louisville
Department of Ophthalmology and Visual Sciences
March 20, 2015
Subjective
CC: blurry vision right eye>left eye, for months
HPI: 57 year old African American male
complains of progressively decreasing distance
vision for months. No pain or history of trauma
History
POH: “pupil anomaly”
PMH: none
Meds: none
Allergies: none
Family Ocular Hx: none
Exam
BCVA:
Pupils:
IOP (mmHg):
EOM:
OD
20/30
OS
20/25
(-2.00+0.25x90)
(-1.00+0.50x90)
inferonasally displaced tear drop pupils
No RAPD
55
45
Full
Full
orthophoric in primary gaze
OD
OS
Inferonasally displaced tear drop shaped pupils OU with inferior
iris atrophy OD
Posterior embryotoxon in the nasal cornea OU
Anterior Segment
SLE:
E/L/L
Conj/sclera
Cornea
AC
Lens
OD
OS
Gonioscopy
angles open, inferior iris strands
extending across angle to insert into
a prominent Schwalbe line OU
WNL OU
White and quiet OU
WNL OU
Deep and quiet OU
NS 2+ CC 1+
NS 1+
Fundus Exam
Optic disc: Significant loss of neuro-retinal rim OD>OS
MVP: wnl
HVF 24-2
OS
OD
Full
Dense inferior and early superior
arcuate scotoma
Assessment

57 year old male with Axenfeld-Rieger syndrome and glaucoma
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DDx:
Iris coloboma
ICE syndrome (unilateral, corectopia, beaten bronze appearance of corneal
-
-
endothelium)
-
Posterior polymorphous corneal dystrophy (bilateral, corectopia,
posterior corneal vesicular-like lesions)

Plan: Travatan and Combigan, new MRx
Axenfeld-Rieger Syndrome

Axenfeld’s anomaly: posterior embryotoxon + abnormal iris
tissue crossing the trabecular meshwork and attaching to the
posterior embryotoxon

Rieger’s anomaly: Axenfeld anomaly + iris changes such as
hypoplastic stroma, a displaced pupil (corectopia) or extra holes
in the iris (polycoria)

Rieger’s Syndrome: Rieger’s anomaly + facial , dental or
umbilical anomalies

Considerable overlap; the three categories represent spectrum of
a single developmental disorder
(Axenfeld-Rieger syndrome: a theory of mechanism and distinctions from the iridocorneal endothelial
syndrome. MB Shields; Trans Am Ophthalmol Soc. 1983; 81: 736–784.)

For instance, iris stromal atrophy may be very subtle in some
patients making it difficult to know whether the term Axenfeld's
anomaly or Rieger's anomaly should be used. Some patients with
ocular findings of Axenfeld’s anomaly have systemic features of
Rieger’s syndrome.

Single diagnostic term of Axenfeld-Rieger syndrome is now
used
Epidemiology/Pathophysiology

Seen in approximately 1/200,000 live births

There is no sex predilection

Defective anterior segment morphogenesis and
systemic abnormalities due to defects in differentiation,
migration, or arrested development of neural crest cells
Genetics

Autosomal dominant but can also occur sporadically

Genetically linked to loci at chromosomes 4q25 (encodes
PITX2), 6p25 (FOXC1), 11 (PAX6) and 13q14 (gene unknown)

Mutations in FOXC1 have been associated with ocular
phenotype of Axenfeld-Rieger Syndrome without the syndromic
features
Clinical features

Photophobia or glare may be a symptom resulting from the
pupillary and iris abnormalities

Developmental abnormalities in the anterior segment:
Corectopia, polycoria, ectropion uveae, posterior embryotoxon,
and increased intraocular pressure

The posterior embryotoxon may not be visible with the slit lamp
examination and may only be visible with gonioscopy
30 year old woman with A-R syndrome, gonioscopy shows
posterior embryotoxon with iris strands attached to it
Source: gonioscopy.org

Glaucoma usually develops in late childhood or adulthood in
50% of cases

Developmental arrest of neural crest cells and their retention
in the anterior chamber angle

Incomplete development of the trabecular meshwork or
Schlemm's canal

Systemically, patients may have:

Craniofacial dysmorphism: hypertelorism, telecanthus,
maxillary hypoplasia, broad, flat nasal bridge

Dental abnormalities: microdontia, hypodontia

Redundant umbilical skin, umbilical hernia

In addition, patients may have hypospadias, anal stenosis,
growth retardation, congenital cardiac outflow tract
malformations

Purpose: To improve the understanding of Axenfeld-Rieger Malfomation (ARM) associated
glaucoma in patients who have known genetic defects in FOXC1 or PITX2

Methods: Clinical data were collected from 126 patients with diagnosed ARM, with
identified mutations in FOXC1 or PITX2 genes

Results: 75% of the patients with ARM who participated in this study had glaucoma that had
developed in adolescence or early adulthood. Patients with PITX2 defects developed
glaucoma at an earlier age and had more severe glaucoma requiring multiple surgeries than
patients with FOXC1. Glaucoma in only 18% of patients with either PITX2 or FOXC1
genetic defects responded to medical or surgical treatment (used solely or in combination)

Conclusions: Patients with PITX2 defects have a more severe prognosis for glaucoma
development. In the present study, current medical therapies do not successfully lower
intraocular pressure or prevent progression of glaucoma in patients with ARM who have
FOXC1 or PITX2 alterations.
References
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BCSC Glaucoma
BCSC External disease and Cornea
www.gonioscopy.org
Axenfeld TH. Embryotoxon cornea posterius. Klin Monatsbl Augenheilkd.
1920;65:381-382.
Rieger H. Beitrage zur Kenntnis seltener Missbildungen der Iris, II: uber Hypoplasie
des Irisvorderblattes mit Verlagerung und entrundung der Pupille. Albrecht von
Graefes Arch Klin Exp Ophthalmol. 1935;133:602-635.
Shields MB. Axenfeld-Rieger syndrome. A theory of mechanism and distinctions from
the iridocorneal endothelial syndrome. Trans Am Ophthalmol Soc. 1983;81:736–84.
Alward WLM: Axenfeld-Rieger syndrome in the age of molecular genetics. Am J
Ophthalmol 2000;130:107-115.
Tsai JC, Grajewski AL. Cardiac valvular disease and Axenfeld-Rieger syndrome. Am J
Ophthalmol. 1994 Aug 15;118(2):255-6.
Thank you