Grand Rounds Conference
Juan P. Fernandez de Castro, MD
University of Louisville
Department of Ophthalmology and Visual Sciences
February 20, 2015
Subjective
CC: Consulted by pediatrics to evaluate corneal opacities
HPI: 2 day old white male with multiple fetal anomalies
including macrocephaly, polyhydramnios and renal
anomalies; underwent c-section for these issues.
Physical exam on birth was abnormal for bilateral
corneal opacities; also cleft lip and palate, anterior
placement of anus, 2 vessel umbilical cord (single
umbilical artery), shortened forearms and absence of
palpable testes. Patient had normal pre-natal
chromosomal analysis.
Past History
POH: Cloudy corneas OU since birth
PMH: No known in-utero insults. Patient following
with MFM (maternal fetal medicine) prior to delivery
Family Hx: No family history of ocular malformations
Allergies: NKDA
Objective
VA (n sc):
Pupils:
OD
OS
Winces to light Winces to light
No view OU
IOP(Squinting):
EOM:
26 mmHg
Full
25 mmHg
Full
Objective
PLE:
External/Lids
WNL
Conj/Sclera
White, clear
Cornea
OD: Diffuse stromal opacification corneal edema, inferior
neovascularization of cornea. No epithelial defect on staining
OS: Very dense diffuse stromal opacification with diffuse
corneal edema. Very pronounced corneal neovascularization
of central cornea. No epithelial defect on staining
External Appearance
External Appearance
Mnemonic for Corneal Opacities
Sclerocornea
 Tears in Descemets
 Ulcers
 Metabolic
 Peters
 Endothelial dystrophy
 Dermoid

Assessment
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2 day old white male with multiple congenital anomalies
including macrocephaly, ventriculomegaly, undescended testes,
single umbilical artery on birth, shortened arms, cleft lip and
palate.
Ocular exam reveals extensive corneal opacification in both eyes
with vascularization of left eye consistent with Peter's anomaly.
In view of the systemic findings the patient's findings are
consistent with Peters Plus Syndrome.
Genetic Testing – B3GALTL
Diagnosis
Peters Plus Syndrome
B3GALTL mutation
(Beta-1,3-glucosyltransferase like)
Follow up 1 month
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Pediatric Ophthalmology
Nystagmus
 IOP WNL
 Bilateral corneal opacities stable


Has had surgical procedures (G-tube x 2 )and
respiratory complications (aspiration
pneumonia) in the past weeks
Peters’ Anomaly
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Albert Peters (Germany, 1862-1938)
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Central corneal leukoma

Variable synechiae between the iris and cornea

Defect in Descemets membrane and the corneal
endothelium
A. Peters, “Uber angeborene defektbildung der descemetschen membran,” Klinische Monatsblätter für
Augenheilkunde, vol. 44, pp. 27–40, 1906.
Classification
All have central corneal opacities

Peters anomaly type I: irido-corneal adhesion
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Peters anomaly type II: cataracts or corneolenticular adhesions

Peters-plus syndrome: Peters anomaly and
short stature, developmental delay, dysmorphic
facial features including cleft lip-palate and
abnormal ears
Townsend W, Font RL, Zimmerman L. Congenital corneal leukoma. Histopathological findings in 19 eyes with central corneal
defects in Descemet’s membrane. Am J Ophthalmol. 1974;77:192.
Multidisciplinary Workup
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Complete ophthalmologic assessment, including ocular ultrasonography
for characterization of the eye anomaly and an assessment for associated
ocular defects
Growth hormone stimulation testing to address the possibility of a treatable
cause of growth delay
For neonates or infants, referral to an infant development program for
appropriate developmental assessment
Echocardiography for congenital heart malformations
Abdominal ultrasound examination for renal anomalies
Cranial imaging with head ultrasound examination or CT scan/MRI for
hydrocephalus and/or structural brain abnormalities
Thyroid function testing in all infants who have not undergone newborn
screening for congenital hypothyroidism
Hearing assessment in a child with cleft palate or speech delay
Medical genetics consultation
Modified from Discovery.lifemapsc.com
Causes
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Incomplete central migration of neural crest
cells
Teratogenic exposures (in-utero infection,
maternal alcoholism)
Glaucoma is common due to incomplete development
of the angle
Chang E, Vislisel J, Larson, SA. Peters Anomaly. EyeRounds.org. June 30, 2014
Available from http://EyeRounds.org/cases/187-Peters-Anomaly.htm
Pathological Gross Appearance
http://www.images.missionforvisionusa.org/
Posterior ulcer of von Hippel
Angle anomalies
Iridocorneal processes
Central defect in Descemets membrane
Posterior stromal layers with adherent
cataractous lens
Albert & Jakobiec's Principles & Practice of Ophthalmology

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Accurate terminology
Genotype/Phenotype correlation
Assessment of prognosis
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With and without intervention
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PRIMARY CORNEAL DISEASE
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Corneal dystrophies
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Corneal dermoid
Peripheral sclerocornea
CYP1B1 cytopathy
SECONDARY CORNEAL DISEASE

Congenital
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Congenital hereditary endothelial dystrophy
Posterior polymorphous corneal dystrophy
Congenital hereditary stromal dystrophy
X-linked endothelial corneal dystrophy
Kerato-irido-lenticular dysgenesis
Irido-trabecular dysgenesis
ACQUIRED
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Infection
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Trauma
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Viral
Bacterial
Forceps injury
Amniocentesis injury
Metabolic
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Mucolipidosis IV
Peters
Iridocorneal Adhesions
Peters I
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Phenotype
Central, eccentric or (rarely) total corneal opacity
Always avascular
Genotype:
Mutations in PITX2, FOXC1, CYP1B1, PAX6
30 eyes after PKP. Mean follow up 78.9 months
90% had clear grafts
>3 years of age: 54% VA better than 20/100
Zaidman GW, Flanagan JK, Furey CC. Long-term visual prognosis in children after corneal transplant surgery for Peters anomaly
type I. Am J Ophthalmol 2007
Peters I
Central opacity
Eccentric opacity, clinical photo and ultrasound biomicroscopy
Lens Fails to Separate from Cornea
Peters II

Developmental failure of separation of the
invaginating lens vesicle from the overlying
surface ectoderm
Vascularized central or total corneal opacity

Early rejection of corneal transplants

Lensectomy leads to vitreous exposure to the new
donor graft
 Treatment remains a challenge

Bhandari R, Ferri S, Whittaker B, et al. Peters anomaly: review of the literature.
Cornea 2011; 30:939–944.
Peters II
Biomicroscopy is equivocal
Intraoperative photos, no lens. Arrow pointing at vitreous
Histology, lens embedded in cornea
Keratoprosthesis
?
Lens separates but fails to form
thereafter
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Total corneal opacification with vascularization
Diagnosed using high-frequency ultrasound or
anterior segment OCT
Unclear if vitreous is abnormal too
Lens separates and forms, but
there is late corneal apposition
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Hypoxia?
Persistent fetal vasculature
Aniridia
Central Avascular Opacity
Anterior Capsule Reflectivity
Lens separates and forms, but
there is late corneal apposition

Removal of lens and peeling of anterior capsule
allows recovery of endothelium. PKP is second
line treatment
Persistent Fetal Vasculature (Pseudo Peters)
Aniridia with keratolenticular touch
Corneal opacities (white), Lens opacities (black)
Lens Fails to Form
Primary Aphakia
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Silver/Gray Cornea
Frequent microphthalmia
FOXE3
Poor PKP outcomes
Pthisis within weeks
 Glaucoma
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Natural history is spontaneous rupture
Lens Fails to Form
Primary Aphakia
Conclusions
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Appropriate anterior segment imaging
Understand the mechanism of the disease
Prognosis with and without intervention
Genetic counseling
Complete workup if syndrome is suspected
Pediatric ophthalmology, cornea, glaucoma
Not all Peters are the same!
References
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Bhandari R, Ferri S, Whittaker B, et al. Peters anomaly: review of the
literature. Cornea 2011; 30:939–944.
Nischal K. A new approach to the classification of neonatal corneal
opacities. Current opinion in ophthalmology [1040-8738]:2012 vol:23 iss:5
pg:344 -54
Lesnik Oberstein SAJ, van Belzen M, Hennekam R. Peters Plus Syndrome.
In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT,
Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA):
University of Washington, Seattle; 1993-2015.
Townsend W, Font RL, Zimmerman L. Congenital corneal leukoma.
Histopathological findings in 19 eyes with central corneal defects in
Descemet’s membrane. Am J Ophthalmol. 1974;77:192